Mice infected with LP-BM5 murine leukemia virus develop lymphadenopathy, splenomegaly, hypergammaglobulinemia, and profound immunosuppression associated with enhanced susceptibility to infection. In this study, molecular genetic analyses of spleen and lymph node cells from infected mice showed the early course of disease was associated with polyclonal proliferations of both B and T cells but that by 12 wk oligoclonal expansions of B or T cells could be detected. When near death, the mice were killed and almost all exhibited clonally restricted populations of B cells, and continuous cultures of B lineage cells were established from three of 19 mice. Histologically, lymph nodes with polyclonal lymphoproliferative lesions were indistinguishable from nodes with clonally restricted populations of cells. However, aggressive immunoblastic lymphomas of characteristic morphology were seen in nonlymphoid organs, particularly in the brain. The demonstration of terminal B cell lymphomas in murine AIDS extends the similarities between this syndrome and AIDS in humans.