Facilitation of yolk-sac carcinoma (YSCa) development in fetectomized rats by the Moloney murine sarcoma virus/murine leukemia virus (Mo-MSV/MLV) complex was found to be closely associated with the presence of Mo-MSV sequences in the genomes of the YSCa cells. The virus-induced YSCas consisted of cells of mono- or oligoclonal origin which always contained in their genomes at least I randomly integrated Mo-MSV provirus. In YSCas which developed in the absence of virus, no rearrangement or amplification of c-mos could be detected. In addition, blot hybridization analysis of cellular RNA failed to detect mos-related RNA in cell lines derived from Mo-MSV-induced as well as from non-virally induced YSCas. The methylation level of c-mos DNA was low in all YSCa cell lines. In contrast, v-mos DNA in cell lines derived from Mo-MSV-induced YSCas was heavily methylated.