Human articular chondrocytes were analyzed for major histocompatibility (MHC) antigens. The cells were obtained by enzymatic digestion of surgical specimens from patients with osteoarthrosis and rheumatoid arthritis having joint replacement. The analyses of Class I and Class II antigens were performed using microcytotoxicity techniques, as with conventional human leukocyte antigen (HLA) typing, and by immunofluorescence on a flow cytometer with monoclonal antibodies. Eighty-five percent of the chondrocytes had strong representation of Class I molecules, and individual specificities for HLA-A, HLA-B, and HLA-C could be detected. Class II antigens generally were not expressed on chondrocytes from noninflammatory states. In osteoarthrosis, some cells expressed HLA-DP and HLA-DQ, whereas in rheumatoid arthritis, there was an increase in the expression of all Class II antigens. Incubation of chondrocytes with gamma-interferon caused the strong induction of HLA-DR and HLA-DP, whereas HLA-DQ expression was largely unaffected. These results have broad implications for tissue transplantation and autoimmune disease.