The fate of input Friend leukemia virus RNA was studied using labeled input virus. The appearance of nuclear RNA-DNA hybrid molecules and the apparent integration of input virion RNA with host cell DNA was studied using a series of inhibitors of DNA or protein synthesis, cell growth conditions, and an intercalating agent. Under all these conditions of infection, little to no viral-specific RNA-DNA hybrid molecules were formed. These data demonstrate that the formation of such RNA-DNA hybrid structures requires conditions of infection that allow provirus synthesis and integration. Furthermore, they suggest that at least a fraction of input virion RNA may transiently become integrated with host cell DNA.