Gene conversion and balancing selection have been invoked to explain the ubiquitous diversity of the antigen-presenting proteins encoded in the vertebrate major histocompatibility complex (MHC). In the present study, direct evidence for over-dominant selection promoting MHC diversity in primates is provided by the observation that, in a large free-ranging population of rhesus macaques, males heterozygous at MHC class II locus Mamu-DQB1 sired significantly more offspring than homozygotes (the male-specific selection coefficient s equals 0.34). This heterozygote advantage appeared to be independent of the actual male Mamu-DQB1 genotype. No similar effect emerged for a captive group of monkeys of similar genetic background but under veterinary care.