The frequencies of the different haplotypes identified at the phenylalanine hydroxylase (PAH) locus were analyzed for both phenylketonuria (PKU) and normal haplotypes of various European, Asiatic, Polynesian and Black American populations. These molecular variants were studied by applying a specific model of multivariate analysis of variance, allowing an estimation of components of variance at different levels of hierarchical subdivisions (intrapopulation, among different geographical groups of populations, and between PKU and normal haplotypes within populations). The results indicate that the PAH polymorphism could be appropriate to study divergence between African, European and Asiatic population groups, but is not sufficient to explain the diversity among European populations. However, the differences in PAH haplotype frequencies between PKU and normal haplotypes are statistically significant over all European populations.