From an evolutionary perspective, human facial attractiveness is proposed to signal mate quality. Using a novel approach to the study of the genetic basis of human preferences for facial features, we investigated whether attractiveness signals mate quality in terms of genetic diversity. Genetic diversity in general has been linked to fitness and reproductive success, and genetic diversity within the major histocompatibility complex (MHC) has been linked to immunocompetence and mate preferences. We asked whether any preference for genetic diversity is specific to MHC diversity or reflects a more general preference for overall genetic diversity. We photographed and genotyped 160 participants using microsatellite markers situated within and outside the MHC, and calculated two measures of genetic diversity: mean heterozygosity and standardized mean d2. Our results suggest a special role for the MHC in female preferences for male faces. MHC heterozygosity positively predicted male attractiveness, and specifically facial averageness, with averageness mediating the MHC-attractiveness relationship. For females, standardized mean d2 at non-MHC loci predicted facial symmetry. Thus, attractive facial characteristics appear to provide visual cues to genetic quality in both males and females, supporting the view that face preferences have been shaped by selection pressures to identify high-quality mates.