Several studies have documented the genetic effects of intraspecific hybridization of cultured and wild Atlantic salmon (Salmo salar L.). However, the effect of salmon aquaculture on wild congeners is not so well understood. Diseases, introduced or increased in incidence by salmon aquaculture activities, may have an impact on co-occurring wild sea trout (Salmo trutta L.), as implied by the steep decline in sea trout numbers in many Irish, Scottish, and Norwegian rivers since the late 1980s, which may be linked to sea lice infestations associated with marine salmonid farming. Our data suggest that salmon farming and ocean ranching can indirectly affect, most likely mediated by disease, the genetics of cohabiting sea trout by reducing variability at major histocompatibility class I genes. We studied samples of DNA extracted from scales of sea trout in the Burrishoole River, in the west of Ireland, before and at intervals during aquaculture activities. In these samples, allelic variation at a microsatellite marker, tightly linked to a locus critical to immune response (Satr-UBA), was compared with variation at six neutral microsatellite loci. A significant decline in allelic richness and gene diversity at the Satr-UBA marker locus, observed since aquaculture started and which may indicate a selective response, was not reflected by similar reductions at neutral loci. Subsequent recovery of variability at the Satr-UBA marker, seen among later samples, may reflect an increased contribution by resident brown trout to the remaining sea trout stock. © 2006 International Council for the Exploration of the Sea.