Several short tandem repeat polymorphism loci at the non-recombining part of the Y chromosome have been described recently and are now widely used for the investigation of the history and the diversity of man. The tetranucleotide repeat polymorphism at the DYS389 locus consists of two repetitive stretches with different numbers of (TCTG)n (TCTA)m repeat units. To study the overall variability of this locus, 768 alleles from males from 10 human populations (two sub-Saharan African, four Caucasoid and four Asian/Amerind populations) were investigated. The alleles found in the populations of different geographic origin exhibited remarkable differences in the number and arrangement of repeats in the two repetitive stretches and up to nine different sequence variants for a single fragment length have been detected. So far 53 different alleles, i.e. haplotypes, have been observed. Analysis of molecular variance (AMOVA) indicates that at least 24.5% of the total genetic variance was found between the populations and that these differences were significant in most pairwise comparisons. We propose a model, in which both founder effects and genetic drift together with single step replication slippage mutations explain the picture of haplotype diversity observed with this single locus.