Serial transfer of spleen cells immune to allogeneic or semi-allogeneic cells induced transferable splenomegaly and general immune deficiencies, including the lack of proliferative responses to T and B cell mitogens and antibody responses to specific antigens. Parallel experiments with spleen cells from mice that had been administered rectally with allogeneic spleen or sperm cells also resulted in a similar immunodeficiency. The immune deficiencies were transferable into normal mice by injection of spleen cells, cellfree extracts, or culture supernatants of spleen cells from immunodeficient mice. The particle responsible for transmission of immunodeficiency appears to be a high m.w. (greater than 2 X 10(6], 1.14 g/ml density agent. These results suggest strongly that serial transfer of lymphocytes immune to alloantigens triggers the release of a transmissible virus-like agent, which results in an immunodeficiency similar to acquired immune deficiency syndrome (AIDS) of humans. Therefore, this system may provide a valuable animal model system for studying AIDS.