We have investigated the allelic polymorphism of the human ABO-secretor locus ( FUT2) in 90 unrelated Papuan-speaking New Guineans (Dani group), 101 admixed New Guineans from Irian Jaya, Indonesia, and 32 New Guineans from Papua New Guinea by DNA sequencing analysis. Whereas the total frequency of various nonfunctional alleles at the FUT2 locus in the worldwide populations so far examined is around 0.5, we have found only one individual heterozygous for a nonfunctional allele in the 90 Dani group members and a frequency of nonfunctional alleles of 0.1-0.2 in the admixed New Guineans. Admixed New Guineans had the Asian-specific null allele se(385) and the characteristic nonfunctional allele se(del2) found in Polynesians. In addition, both New Guinean populations had unique functional alleles ( Se(375) and Se(400)) with high frequencies (0.11-0.37); these are absent in other populations of the world except for African and Samoan populations. The Se(375) allele had G and C at positions 1009 and 1011 of the 3' untranslated region, respectively, whereas all other FUT2 alleles found so far in the world, except for se(428), have 1009A and 1011T. The Se(375) allele found in Africans has 1009G and 1011T, or 1009A and 1011T. Corresponding positions of nonhuman primates have G and C, suggesting that the Se(375) allele is one of the ancestral alleles, reflecting the early human migration from Africa to New Guinea and the long isolation of Dani populations from neighboring populations.