Recombinant mink cell focus-inducing (MCF) murine leukemic viruses, as well as ecotropic and xenotropic viruses, were tested for ability to accelerate or cause development of lymphoma in AKR and other strains of mice. Of the three classes of virus isolated from AKR, only the MCF viruses were able to accelerate development of AKR lymphoma. This fully supports the idea that the MCF viruses are the proximal cause of spontaneous AKR lymphoma. MCF lymphomagenicity was strain specific, however, in that AKR MCF viruses did not induce lymphomas in many murine strains; they were moderately lymphomagenic in C3H/Bi mice and in National Institutes of Health Swiss partially congenic for Akv-1 or Akv-2. In contrast, MCF viruses from nonthymic hematopoietic neoplasms of C3H/Fg, BALB/c, or mice partially congenic for ecotropic virus loci (Akv-1, Akv-2, Fgv-1, C58v-1, and C58v-2) were not able to accelerate or cause lymphomia in AKR or any other mouse strain tested, including some of the strains of origin. MCF lymphomagenicity correlated with thymic origin in the virus and with ability to replicate in the thymus.