A multi-centre, double-blind, randomized parallel group study was undertaken in general practice to compare the efficacy and tolerability of the new non-steroidal anti-inflammatory drug acemetacin with indomethacin in patients suffering from rheumatoid arthritis. One hundred and seventy-three patients were treated for 6 weeks with either acemetacin or indomethacin. Most patients received 120 mg acemetacin per day or 100 mg indomethacin per day. Both drugs produced statistically significant improvements in the primary efficacy variables, ARA articular index, grip strength, and morning stiffness. Overall response to acemetacin was slightly superior to indomethacin, but was not statistically significant. With regard to tolerability, the incidence and severity of gastro-intestinal adverse effects was significantly less with acemetacin than with indomethacin, and central nervous system adverse effects were also markedly fewer. It was concluded that acemetacin was at least as effective as indomethacin in the treatment of rheumatoid arthritis, but has significant advantages in terms of tolerability.