Intraperitoneal administration of group A streptococcal cell walls to rats induces an acute arthritis that resolves and is followed by a chronic lesion. The effect of low dose methotrexate, D-penicillamine and gold thioglucose has been investigated in this model. Whereas D-penicillamine and gold thioglucose had no effect on the hind paw inflammation and joint destruction (radiological assessment) associated with the lesion, methotrexate treatment suppressed both of these variables. Spleen cells derived from cell wall treated arthritic rats were hyporesponsive to concanavalin A (Con-A) and were deficient in the synthesis of interleukin 2 (IL-2). Spleen cells derived from methotrexate treated rats exhibited an improved response to Con-A and their ability to synthesize IL-2 was significantly enhanced.