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To assess the value of bovine immunodeficiency virus (BIV) infection as a model for human immunodeficiency virus (HIV) infection in man, we studied the impairment of certain immunologic functions in New Zealand white rabbits experimentally infected with an uncloned virulent isolate of the virus, BIV R29. Serum samples were tested by Western blot for the presence and persistence of antibody production. The T- and B-lymphocyte function was studied by evaluation of the blastogenic responsiveness to concanavalin A (Con A) and to dextran sulfate (DxS). All infected rabbits seroconverted to BIV antigens within 2 to 4 weeks postinfection (p.i.) The BIV was isolated from the peripheral blood lymphocytes (PBLs) of 13 of 17 rabbits (77%) early in the infection and also from 5 of 17 hyperplastic mesenteric lymph nodes (29%) and 10 of 17 spleens (59%) during the chronic stage of infection. Seven of 17 BIV-infected rabbits (41%) developed marked immunodepression 2 to 5 months p.i., and later, 5 exhibited a rapidly progressive disease with anorexia, weight loss, neurologic impairment, splenomegaly, and mesenteric lymphadenopathy. These data underline the value of the BIV model for studying HIV pathogenesis in vivo and the development of interventional strategies for AIDS.