Forty patients with osteoarthritis of the hips or knees entered a double-blind crossover study, in which 50 mg t.i.d. indomethacin was compared to a single daily dose of 600 mg benoxaprofen. Patients were randomly allocated to either indomethacin or benoxaprofen for four weeks and then transferred to the alternate drug without a washout period. Thirty-one patients completed the entire trial period. Both indomethacin and benoxaprofen led to a statistically significant improvement (alpha less than or equal to 0.05) of the subjective (measured by a pain score) and the objective joint status (range of motion evaluation) as compared to the pretreatment status. With regard to efficacy, there was no statistically significant difference between the two drugs. Benoxaprofen proved to be the better tolerated compound, causing four dropouts. Six patients were excluded from the indomethacin treatment due to severe gastrointestinal side effects. There also was a higher number of other side effects with indomethacin, but none severe enough to discontinue treatment. With the doses used, both compounds proved to be similar in efficacy in osteoarthritic conditions although benoxaprofen was the better tolerated drug.