We studied the population genetic structure of 360 and 1247 adult Schistosoma mansoni using seven microsatellite and seven random amplified polymorphic DNA (RAPD) markers, respectively. Parasites were collected from their natural definitive host Rattus rattus in Guadeloupe (West Indies). We found a sex-specific genetic structure, a pattern never before reported in a parasitic organism. Male genotypes were more randomly distributed among rats than female genotypes. This interpretation was consistent with a lower differentiation between hosts for males relative to females, the higher genetic similarity between females in the same host and the observed local (i.e. within-individual-host) differences in allele frequencies between the two sexes. We discuss our results using ecological and immunological perspectives on host–parasite relationships. These results change our view on the epidemiology of schistosomiasis, a serious disease affecting humans in African and American intertropical zones.