A series of five experiments on histocompatibility gene mutation as detected by tail-skin graft tests in isogenic mice has been completed. To explain the results it is hypothesized that the observed histocompatibility changes were the result of the incorporation of viral genomes into germinal cells of parents in a manner paralleling the phenomenon of lysogeny in bacteria. This hypothesis would explain why most changes were gains in antigen, why paternal X-irradiation had no detectable augmenting affect on incidence, but why the environment in which the parents were born and raised did seem to affect the incidence. The hypothesis is extended to explain the origin and function of the histocompatibility and blood-group genes.