To develop rabbit as a model system for HIV-associated neuropathogenesis and to determine if HIV-1,br (an isolate from the brain of an AIDS dementia patient, Virology, 1989;168:79-89) has unique neuropathic characteristics, a 36-day-old rabbit was inoculated intraperitoneally with cell-free HIV-1,br. The rabbit was treated with thioglycollate four days prior to inoculation and was then bled for serum and lymphocytes approximately at biweekly intervals. The rabbit was sacrificed 90-days after inoculation and its brain, spleen, thymus and adrenals were removed. Collected lymphocytes and tissues were tested for markers of infection and sera were tested for the presence of antibodies to HIV-1. Lymphocytes were negative for the presence of HIV-1 in cocultivation assays. Of the tissues tested, only the brain was positive for the presence of HIV-1 in cocultivation, although spleen, thymus and adrenals were weakly positive by PCR. The brain had the highest level of HIV-1 DNA. RNA-PCR showed the presence of viral RNA in the brain samples. The serum samples were negative for the presence of HIV-1 specific antibodies both by the ELISA and Western blot methods. Amplified gag gene fragment was molecularly cloned and sequenced which proved unequivocally that HIV-1 was present in the brain. In conclusion, HIV-1,br established infection in the brain in the absence of detectable seroconversion. Currently, studies are planned to investigate the incidence of brain infection with HIV-1,br and also to examine the relative predilection of HIV-1,br for the rabbit brain as compared to the other HIV-1 isolates.