Genes involved in major biological functions, such as reproductive or cognitive functions, are choice targets for natural selection. However, the extent to which these genes are affected by selective pressures remains undefined. The apparent clustering of these genes on sex chromosomes makes this genomic region an attractive model system to study the effects of evolutionary forces. In the present study, we analysed the genetic diversity of a X-linked microsatellite in 1410 X-chromosomes from 10 different human populations. Allelic frequency distributions revealed an unexpected discrepancy between the sexes. By evaluating the different scenarios that could have led to this pattern, we show that sex-specific selection on the tightly linked VCX gene could be the most likely cause of such a distortion.