Two strains of feline leukemia virus, two endogenous feline type-C viruses (RD/CCC group), several endogenous and laboratory strains of murine "leukemia" virus, two rat viruses, two primate viruses (woolly monkey and gibbon ape), as well as hamster, pig, and avian type-C viruses were examined for their relatedness to one another by molecular hybridization. The extent of nucleic-acid homology was determined by hybridization of the various viral RNAs to a [(3)H]DNA product synthesized from each virus. Among the murine type-C viruses (Rauscher, Kirsten, AT-124, and endogenous BALB/c virus) a high degree of homology is observed, although the viruses are not identical. The two primate viruses are also closely related to one another. The feline, rat, hamster, and pig endogenous viruses can be readily distinguished from one another and from the murine and primate viruses since their DNA products share very little or no nucleic-acid homology. However, the murine and primate type-C virus groups possess a surprising degree of relatedness. Feline type-C viruses fall into two distinct groups, the feline leukemia virus group and the RD-114/CCC group, with little detectable nucleic-acid homology between them. Infection of feline or rat cells with type-C virus results in production of the endogenous type-C virus of the species along with the infecting virus.