BALB/c mice neonatally injected with (BALB/c X C57BL/6)F1 hybrid spleen cells develop host-versus-graft disease (HVGD) with immunopathological features characteristic of either systemic lupus erythematosus (SLE), or immunoblastic lymphadenopathy (IBL) in man. HVGD mice manifest polyclonal hypergammaglobulinemia with various autoantibodies, generalized lymphadenopathy, hepatosplenomegaly, immune complex glomerulonephritis and evolve in the end to malignant lymphoma. The necessary prerequisite for HVGD induction between donor and host can be summarized as follows: Histoincompatibilities in the H-2 region between donor and host are needed; predominant F1 donor cells needed for HVGD induction are, if not sole, steroid resistant, nylon wool nonadherent and Thy-1 positive T cells; the role of donor T cells is not only to present H-2 complex to the host, but also to interact with and proliferate in the host; strain differences are found for the susceptibility of HVGD induction in the host. It has been found that HVGD evolves to a malignant lymphoma of host T cell origin. The HVGD mouse model may, therefore, contribute to the understanding of the cell to cell interactions at work in the pathogenesis of IBL, as well as SLE, in man.