M813 is a type-C murine leukemia virus (MuLV) isolated from the Asian rodent Mus cervicolor. We have recently demonstrated that M813 defines a distinct MuLV receptor interference group. Here we show that M813 rapidly induces fusion of MuLV-expressing fibroblasts from "without," with syncytia being observed within 1 h after exposure to virus. Infection of fibroblasts with MuLV from all tested receptor-interference groups imparts susceptibility to M813-induced fusion, provided the cells also express the M813 receptor. Syncytium induction is also observed in vivo; mice infected with M813 develop a peripheral T-cell lymphoma, which is associated with large multinucleated cells of macrophage origin. A recombinant Moloney MuLV/M813 chimeric virus demonstrated that syncytium induction is a function of the Env SU protein. We postulate that the highly fusogenic property of M813 is attributable to either its unique receptor usage or sequences in the proline-rich domain of the Env protein.