Alloalbuminemia is rare and has a cumulative frequency of only approximately 1 in 3,000 in Europeans and Japanese. The worldwide ethnic and geographic distribution of certain albumin genetic variants appears to be nonrandom. Moreover, we have found that structurally identical variants may occur at different frequencies in ethnically distinct populations, presumably owing to independent mutations. In this study, albumin B and two types of proalbumins, which as a group are the most common European albumin variants, have also been found in Asians. We have identified the amino acid substitution characteristic of albumin B (glutamic acid----lysine at position 570) in alloalbumins from six unrelated individuals of five different European descents and also in two Japanese and one Cambodian. The two types of proalbumins most common in Europe (Lille type, arginine----histidine at position -2; Christchurch type, arginine----glutamic acid at position -1) also occur in Japan. These results provide evidence for independent mutations at single sites in the albumin genome. The clustering of these and of several other amino acid exchanges in certain regions of the albumin molecule suggests two possibilities: that certain sites are hypermutable or that mutants involving certain sites are more subject to selection than mutants involving others.