A target cell assay based on the formation of infectious centers (IC) was used to characterize the Fv-2resistance gene of mice. Dose-response curves were obtained for the number of IC generated from incubated mixtures of bone-marrow cells and Friend virus (FV). The hemopoietic stimulus of bleeding increased the frequency of potential "target" cells capable of forming IC in DBA/2 but not in D2.Fv-2r mice; however, even without the bleeding stimulus D2.Fv-2r mice contained fewer target cells in their bone marrow than DBA/2 mice. During the first 48 h postinfection a massive dose of FV overcame the inhibitory effect of the FV-2r gene as measured by the release of FV from the spleen. However, the concentration of IC recoverable from the spleens of these infected mice was still much lower in the D2.Fv-2r strain. When irradiated F1 hybrid hosts were used as recipients for the proliferation of infected donor cells, splenic IC were not generated as efficiently from infected bone-marrow cells of D2.Fv-2r origin as from those of DBA/2 origin. However, the amounts of SFFV recoverable were approximately the same. Similarly, after in vitro infection there was no great difference between the amounts of SFFV released from bone-marrow cells of DBA/2 and D2.Fv-2r mice. We conclude that the primary effect of the Fv-2r gene may be to inhibit the formation and proliferation of IC in vivo, and that SFFV replication could be inhibited secondarily.