In a double-blind study, the efficacy and tolerability of nimesulide 200mg/day, administered orally, was compared with etodolac 600mg/day in the treatment, for 3 months, of 200 patients suffering from osteoarthritis of the knee. Although spontaneous pain showed a significant improvement during the course of the study, there was no difference in the efficacy of either compound. Similarly, there was a progressive and significant reduction in the Lequesne functional index although no statistical difference was found between nimesulide and etodolac. The physician's overall assessment of efficacy was significantly in favour of nimesulide but the same assessment for patients who completed all 12 weeks showed no such bias. Adverse events (AEs) were generally mild or moderate and were commonly gastrointestinal in origin. There was no difference in the rate of incidence of AEs and, with the exception of week 8 where etodolac was apparently better tolerated, there were no statistical differences in tolerability between the two therapies.