In most human populations, the ability to digest lactose contained in milk usually disappears in childhood, but in European-derived populations, lactase activity frequently persists into adulthood (Scrimshaw and Murray Scrimshaw and Murray, 1988Scrimshaw N Murray E The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance.Am J Clin Nutr. 1988; 48: 1079-1159PubMed Google Scholar). It has been suggested (Cavalli-Sforza Cavalli-Sforza, 1973Cavalli-Sforza L Analytic review: some current problems of population genetics.Am J Hum Genet. 1973; 25: 82-104PubMed Google Scholar; Hollox et al. Hollox et al., 2001Hollox EJ Poulter M Zvarik M Ferak V Krause A Jenkins T Saha N Kozlov AI Swallow DM Lactase haplotype diversity in the Old World.Am J Hum Genet. 2001; 68: 160-172Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar; Enattah et al. Enattah et al., 2002Enattah NS Sahi T Savilahti E Terwilliger JD Peltonen L Jarvela I Identification of a variant associated with adult-type hypolactasia.Nat Genet. 2002; 30: 233-237Crossref PubMed Scopus (768) Google Scholar; Poulter et al. Poulter et al., 2003Poulter M Hollox E Harvey CB Mulcare C Peuhkuri K Kajander K Sarner M Korpela R Swallow DM The causal element for the lactase persistence/non-persistence polymorphism is located in a 1 Mb region of linkage disequilibrium in Europeans.Ann Hum Genet. 2003; 67: 298-311Crossref PubMed Scopus (103) Google Scholar) that a selective advantage based on additional nutrition from dairy explains these genetically determined population differences (Simoons Simoons, 1970Simoons F Primary adult lactose intolerance and the milking habit: a problem in biologic and cultural interrelations. II. A culture historical hypothesis.Am J Dig Dis. 1970; 15: 695-710Crossref PubMed Scopus (203) Google Scholar; Kretchmer Kretchmer, 1971Kretchmer N Memorial lecture: lactose and lactase—a historical perspective.Gastroenterology. 1971; 61: 805-813Abstract Full Text PDF PubMed Google Scholar; Scrimshaw and Murray Scrimshaw and Murray, 1988Scrimshaw N Murray E The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance.Am J Clin Nutr. 1988; 48: 1079-1159PubMed Google Scholar; Enattah et al. Enattah et al., 2002Enattah NS Sahi T Savilahti E Terwilliger JD Peltonen L Jarvela I Identification of a variant associated with adult-type hypolactasia.Nat Genet. 2002; 30: 233-237Crossref PubMed Scopus (768) Google Scholar), but formal population-genetics–based evidence of selection has not yet been provided. To assess the population-genetics evidence for selection, we typed 101 single-nucleotide polymorphisms covering 3.2 Mb around the lactase gene. In northern European–derived populations, two alleles that are tightly associated with lactase persistence (Enattah et al. Enattah et al., 2002Enattah NS Sahi T Savilahti E Terwilliger JD Peltonen L Jarvela I Identification of a variant associated with adult-type hypolactasia.Nat Genet. 2002; 30: 233-237Crossref PubMed Scopus (768) Google Scholar) uniquely mark a common (∼77%) haplotype that extends largely undisrupted for >1 Mb. We provide two new lines of genetic evidence that this long, common haplotype arose rapidly due to recent selection: (1) by use of the traditional FST measure and a novel test based on pexcess, we demonstrate large frequency differences among populations for the persistence-associated markers and for flanking markers throughout the haplotype, and (2) we show that the haplotype is unusually long, given its high frequency—a hallmark of recent selection. We estimate that strong selection occurred within the past 5,000–10,000 years, consistent with an advantage to lactase persistence in the setting of dairy farming; the signals of selection we observe are among the strongest yet seen for any gene in the genome. In most human populations, the ability to digest lactose contained in milk usually disappears in childhood, but in European-derived populations, lactase activity frequently persists into adulthood (Scrimshaw and Murray Scrimshaw and Murray, 1988Scrimshaw N Murray E The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance.Am J Clin Nutr. 1988; 48: 1079-1159PubMed Google Scholar). It has been suggested (Cavalli-Sforza Cavalli-Sforza, 1973Cavalli-Sforza L Analytic review: some current problems of population genetics.Am J Hum Genet. 1973; 25: 82-104PubMed Google Scholar; Hollox et al. Hollox et al., 2001Hollox EJ Poulter M Zvarik M Ferak V Krause A Jenkins T Saha N Kozlov AI Swallow DM Lactase haplotype diversity in the Old World.Am J Hum Genet. 2001; 68: 160-172Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar; Enattah et al. Enattah et al., 2002Enattah NS Sahi T Savilahti E Terwilliger JD Peltonen L Jarvela I Identification of a variant associated with adult-type hypolactasia.Nat Genet. 2002; 30: 233-237Crossref PubMed Scopus (768) Google Scholar; Poulter et al. Poulter et al., 2003Poulter M Hollox E Harvey CB Mulcare C Peuhkuri K Kajander K Sarner M Korpela R Swallow DM The causal element for the lactase persistence/non-persistence polymorphism is located in a 1 Mb region of linkage disequilibrium in Europeans.Ann Hum Genet. 2003; 67: 298-311Crossref PubMed Scopus (103) Google Scholar) that a selective advantage based on additional nutrition from dairy explains these genetically determined population differences (Simoons Simoons, 1970Simoons F Primary adult lactose intolerance and the milking habit: a problem in biologic and cultural interrelations. II. A culture historical hypothesis.Am J Dig Dis. 1970; 15: 695-710Crossref PubMed Scopus (203) Google Scholar; Kretchmer Kretchmer, 1971Kretchmer N Memorial lecture: lactose and lactase—a historical perspective.Gastroenterology. 1971; 61: 805-813Abstract Full Text PDF PubMed Google Scholar; Scrimshaw and Murray Scrimshaw and Murray, 1988Scrimshaw N Murray E The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance.Am J Clin Nutr. 1988; 48: 1079-1159PubMed Google Scholar; Enattah et al. Enattah et al., 2002Enattah NS Sahi T Savilahti E Terwilliger JD Peltonen L Jarvela I Identification of a variant associated with adult-type hypolactasia.Nat Genet. 2002; 30: 233-237Crossref PubMed Scopus (768) Google Scholar), but formal population-genetics–based evidence of selection has not yet been provided. To assess the population-genetics evidence for selection, we typed 101 single-nucleotide polymorphisms covering 3.2 Mb around the lactase gene. In northern European–derived populations, two alleles that are tightly associated with lactase persistence (Enattah et al. Enattah et al., 2002Enattah NS Sahi T Savilahti E Terwilliger JD Peltonen L Jarvela I Identification of a variant associated with adult-type hypolactasia.Nat Genet. 2002; 30: 233-237Crossref PubMed Scopus (768) Google Scholar) uniquely mark a common (∼77%) haplotype that extends largely undisrupted for >1 Mb. We provide two new lines of genetic evidence that this long, common haplotype arose rapidly due to recent selection: (1) by use of the traditional FST measure and a novel test based on pexcess, we demonstrate large frequency differences among populations for the persistence-associated markers and for flanking markers throughout the haplotype, and (2) we show that the haplotype is unusually long, given its high frequency—a hallmark of recent selection. We estimate that strong selection occurred within the past 5,000–10,000 years, consistent with an advantage to lactase persistence in the setting of dairy farming; the signals of selection we observe are among the strongest yet seen for any gene in the genome.