Antigen-induced arthritis (AIA) in mice occurs after immunization and a subsequent intra-articular injection with methylated bovine serum albumin (mBSA). The role of T lymphocytes in the adoptive transfer of susceptibility to AIA into SCID mice was investigated. Pooled spleen and lymph node cells from immunized syngeneic or allogeneic donor mice, isolated either before or after the induction of arthritis, could transfer the capacity both to develop arthritis and to produce antibodies to mBSA, collagen type II and cartilage proteoglycans into SCID mice. The intra-articular injection of mBSA in responder animals, immediately after the cell transfer, resulted in a chronic arthritis in the induced joint. The histologic examination revealed synovial hyperplasia, mononuclear infiltration of the synovial membrane, exudation of polymorphonuclear leucocytes into the joint space, and chondrocyte death. The depletion of CD4+ T cells before transfer prevented the manifestation of arthritis in SCID mice, with a concomitant decrease in antibody levels to mBSA, collagen type II and cartilage proteoglycans. In contrast, removal of CD8+ T cells did not significantly affect the transfer of arthritis into SCID mice. The results demonstrate an essential role of CD4+ T cells in the pathogenesis of AIA, whereas CD8+ T cells do not seem to be required for the induction and perpetuation of this disease.