To identify possible retrovirus related synovial antigens the immunohistochemistry of rheumatoid synovial tissues was performed. Paraffin-embedded synovial tissues (group 1) from patients with rheumatoid arthritis (RA) were studied with an immunogold technique using monoclonal antibodies against p17 and p24 of the human immunodeficiency virus type I (HIV-I). Immunoreactivity for HIV-I p17 and p24 antigens was detected in 52% and 54% (n=23) of the paraffin-embedded RA specimen, respectively. Immunofluorescence examination of fresh rheumatoid synovial tissues (group 2) revealed reactivity in 60% (n=10) of the cases. RA patients (group 2) whose synovial tissues were reactive by immunofluorescence were seronegative to HIV-I antigens as determined by ELISA and immunoblotting. In one case, reactive tissue processed for immunoelectron microscopy utilizing the immunogold technique, a virus-like structure HIV-I p1. (diameter of 100nm) with an electron-dense core surrounded by a membrane was labeled with antibody to HIV-I p17 reactive electron-dense particles similar in size but lacking membranous structures were also detected in the cytoplasm of 2 different rheumatoid synovial tissues. HIV-I related antigens can be detected in the majority of the rheumatoid synovial tissues in the absence of circulating antibodies to HIV-I. We conclude that HIV-I related antigens might play a role in the pathogenesis of rheumatoid arthritis.