RF/J mice carry three endogenous ecotropic murine leukemia proviruses designated Emv-1, Emv-16, and Emv-17. Two of these proviruses, Emv-16 and Emv-17, are tightly linked and segregate with the high viremia phenotype in backcrossed mice. During the derivation of an SWR/J strain congenic for Emv-16 and Emv-17, we found that many of the progeny derived from female virus carriers acquired new germline ecotropic proviruses. Additional genetic crosses suggested that these proviruses are acquired early in development by virus infection and that this strain combination is particularly susceptible to these events. The frequency of proviral acquisition was only about 10-fold lower than the frequency of P element acquisition in dysgenic crosses of Drosophila melanogaster. Since virus integration in these hybrids occurs at many different sites, these types of hybrids may ultimately be useful for generating virally induced mutations that are amenable to study at the molecular level.