The therapeutic effects of a variety of agents on established lesions of type II collagen arthritis in rats were tested. Drug activity was determined using an Arthritic Index, which consisted of a rank score ranging from 0 to 8 (0 to 4 in each hind paw) based on hind paw swelling and redness, and by measuring titers of antibody to type II collagen. Four of five non-steroidal antiinflammatory drugs (NSAIDs), phenylbutazone, benoxaprofen, indomethacin and isoxicam, reduced swelling. Of the NSAIDs, only acetylsalicylic acid was inactive. None of these drugs reduced levels of antibody to type II collagen as determined by an ELISA procedure. One of two immunosuppressive drugs, cyclophosphamide, and a steroid, hydrocortisone acetate, significantly inhibited hind paw inflammation. The other immunosuppressive, azathioprine, did not significantly reduce swelling. Also, cyclophosphamide lowered levels of antibody to type II collagen. Five antirheumatic agents, auranofin, levamisole, D-penicillamine, chloroquine and aurothioglucose, were tested and none inhibited the disease process. Of these five, only auranofin inhibited antibody titer to type II collagen. In conclusion, although rat type II collagen arthritis did not detect standard antirheumatic drugs, this model detected the activity of several standard NSAIDs, an immunosuppressive, and a steroid. In addition, the level of antibody to type II collagen was neither a selective nor sensitive indicator of the efficacy of standard antiarthritic agents.