Sensitivity to the odor of 5-androst-16-en-3-one (androstenone), a testosterone metabolite, shows wide variations among unrelated individuals. Analysis of correlations in sensitivity between monozygotic twin pairs, dizygotic twin pairs, and nontwin sib pairs now shows that at least a portion of this variation is genetically determined. However, although data from some mouse studies have suggested a relationship between olfaction and the murine histocompatibility system (H-2), we were unable to demonstrate any role of the human HLA system in explaining the wide individual variations in human sensitivity to androstenone. An additional analysis of HLA antigens among 61 human mating pairs also provided no evidence that HLA phenotypes play a role in human mating preference. These data fail to support a role for the human HLA system in the recognition of an odorant of potential biological significance.