SummaryMice of the C3H strain, which are genetically resistant to mouse hepatitis virus, MHV(PRI), became highly susceptible to that virus when preinfected with the murine blood parasite, Eperythrozoon coccoides (E. coccoides). Peak virus titers and deaths occurred 2 or more days later in E. coccoides-infeeted C3H mice than those events in genetically susceptible Princeton (PRI) mice. Growth curves and infectivity analyses of progeny virus in cultures of susceptible PRI and resistant C3H cells demonstrated that MHV(PI~I) itself multiplied to high titer in E. coccoides-infected Can mice. Variant virus, MttV(C3H), was also produced, but appeared later in the infection and comprised on]y a small fraction of the progeny virus. On subsequent passage of progeny virus in E. coccoides-infected C3H mice, MHV(PRI) continued to be produced far in excess of MHV(C3H). In normal (E. coccoides-free) C3H mice, progeny virus caused deaths or lesions indicative of the presence of variant virus, and the latter was recovered at a high titer. The action of E. coccoides, whereby MHV(PRI) multiplication is initiated in genetically resistant (nonpermissive) can cells, could not be reproduced in vitro.