Host genetic influences on fetal susceptibility to murine cytomegalovirus after maternal or fetal infection. Genetically determined resistance to murine cytomegalovirus is observed in adult mice and is mediated in part by genes of the H-2 complex, with the H-2k haplotype conferring resistance. This model was used to examine the effect of primary maternal infection on fetal outcome. The severity of fetal growth retardation and death after primary maternal infection on day 8 of pregnancy was found to be genetically determined. Fetal viability and weight were significantly lower in infected BALB/c mothers (H-2d) than in CBA(H-2k) and BALB.K(H-2k) mothers. However, fetal infection was not detected, suggesting that the resistance mechanisms operate at the level of the mother or placenta. By directly inoculating fetuses in utero, it was shown that genetic factors in the fetus can influence the level of fetal infection and viability. These results point to the possibility that host genetic factors may modulate maternal and fetal cytomegalovirus infections in humans. 