The weekly intraperitoneal injection of rat erythrocytes into mice induces both a stable autoimmune state, as judged by the appearance of anti-mouse erythrocyte autoantibody and suppressor T cells capable of regulating this response; the latter being demonstrable only in a subsequent transfer system. This autoimmune response and the parallel anti-rat erythrocyte response were both insensitive to exogenous prostaglandin E2 (PGE2). The administration of prostaglandin synthetase inhibitors (indomethacin or aspirin) to mice undergoing immunization with rat erythrocytes had no effect on the anti-rat response, yet mildly exacerbated the onset of the autoimmune state and potently inhibited the generation of suppressor cells. Furthermore the administration of these drugs to recipients of suppressor cells virtually abrogated suppressor cell activity. These observations imply that both the generation and effector function of these suppressor cells may be modulated by prostaglandin synthetase inhibitors while at the same time T helper and B cell functions remain unimpaired.