The influence of the major mouse histocompatibility gene complex (H-2) on the response of mice to Friend leukemia virus was studied in F1 congenic mice differing only at genes within the H-2 complex. F1 mice which were H-2b/b had a high incidence of recovery from splenomegaly compared to H-2b/d or H-2b/a mice. In mice with recombinations within the H-2 complex a gene (designated RFV-1), responsible for the Friend virus recovery effect, was found to map near or within the D region of serologically detectable transplantation antigens. Because the incidence of recovery was much higher in F1 H-2b/b mice than in parental H-2b/b mice, other non-H-2 host genetic factors also appear to be important to expression of recovery in H-2b/b F1 mice. The mechanisms of action of these genes remain unknown.