We studied the ability of dimethyl sulfoxide (DMSO) to influence the course of an experimental model of inflammatory arthritis. A Dumonde-Glynn model of arthritis was induced in both tibio-femoral joints of 10 rabbits, using ovalbumin as the immunogen. At one month post induction of the arthritis, the right tibio-femoral joint of 6 animals was treated for 3 months with topical 80% DMSO--1 g/kg body weight applied to the shaved skin for 5 out of 7 days each week. In another 4 animals, the right tibio-femoral joint was injected with 0.5 ml of 80% DMSO at one month post induction of the arthritis. Joint radiographs were taken at monthly intervals. The rabbits were sequentially sacrificed and the joint tissues evaluated by a blinded observer. Neither the topical DMSO nor the intraarticular DMSO treated joints showed any favorable responses to therapy; in fact the topically treated joints exhibited somewhat more inflammatory and destructive changes than the untreated joints. However the repeated injection of DMSO into normal joints did not, of itself, produce any deleterious effects. This study indicates a need to assess more thoroughly a possible deleterious effect of DMSO on the course of untreated inflammatory arthritis.