We investigated the effect of cyclosporin A, an inhibitor of T helper/inducer lymphocyte activation, on the development of streptococcal cell wall-induced arthritis and hepatic granulomas in female LEW/N rats. Continuous daily treatment with cyclosporin A, begun either 24 hours before or 7-12 days after streptococcal cell wall administration and continued for 6 weeks, resulted in significant inhibition of the chronic proliferative, erosive synovitis and total inhibition of hepatic granuloma formation. When cyclosporin A was stopped at 6 weeks, its effects continued for at least another 5 weeks, demonstrating long-term benefit without continued administration of the drug. In contrast, therapy given only during the acute phases of the experimental disease (days 1-12) did not inhibit the development of chronic disease. Cyclosporin A had no apparent effects on streptococcal cell wall antigen distribution or persistence in tissues. These data provide additional evidence of an important role for the T helper/inducer lymphocyte in the experimental model and suggest that cyclosporin A may be a useful probe in defining molecular and cellular processes involved in chronic proliferative and erosive synovitis.