A battery of drugs which are commonly used as therapeutic agents for arthritis was tested for effects on the inflammatory and immunological responses of DBA/1J mice, after immunization with type II collagen. All the drugs were tested at more than one dosage. The mice were protected from the development of arthritis by treatment with paramethasone (0.25 mg/kg/day) or cyclophosphamide (5 mg/kg/day). The nonsteroidal anti-inflammatory drugs used in these studies, viz. aspirin (200 mg/kg/day), benoxaprofen (100 mg/kg/day) and naproxen (200 mg/kg/day), had no significant effect on the joint involvement, although naproxen and benoxaprofen at these high doses caused some reduction of immune responses of mice to collagen. Chloroquine (100 mg/kg/day), levamisol (50 mg/kg/day) and gold chlorophosphene (5 mg/kg/day) had no effect on the inflammatory or humoral response, while treatment with D-penicillamine (100 mg/kg/day) led to an early onset of arthritis in mice. These data suggest that the type II collagen-induced mouse arthritis model may not be highly suitable for detection of the traditional nonsteroidal anti-inflammatory class of drugs or the anti-rheumatic drugs, although the possibility remains that some new and novel immunosuppressive agents may be detected with this model.