The purpose of this study was to investigate the effects of cyclosporine A (CSA) and methotrexate (MTX) as potential immunomodulators in a nonestablished adjuvant arthritis (AA) model. Non-injected hind paw volumes were reduced when AA rats were treated for 18 days with CSA (100% at 10 mg/kg) or MTX (100% at 0.1 mg/kg). Body weights of drug treated AA rats were increased above untreated AA rats and were similar to non-arthritic controls. AA rats show elevated T helper (W3/25+)/T suppressor (OX 8+) cell ratios (2.0 vs. 3.1, p less than 0.01). The immunomodulators tested all returned these elevated ratios to control non-arthritic levels. Similarly, these drugs returned the reduced mitogen responses and elevated blood granulocyte numbers toward normal non-arthritic control values.