A double-blind clinical trial was carried out in 69 rheumatic in-patients to compare the efficacy and tolerance of a new, non-steroidal anti-inflammatory agent, protacine, with that of indomethacin. Patients received either 150 mg protacine or 50 mg indomethacin 3-times daily for 21 days. The time course of symptoms was recorded by semiquantitative scoring, as were side-effects. Uropepsinogen excretion, occult blood in faeces and standard physiological parameters were also monitored. Protacine globally decreased symptom scores by 58.5% and indomethacin by 24.3% (p less than 0.001). The computed time to reduce symptom scores by 50% was 17.2 days with protacine as compared to 39.2 days with indomethacin (p less than 0.001). Physiological parameters did not change, except white blood cells which decreased after protacine (each subject however, remaining well within the physiological range) and erythrocyte sedimentation rate, which decreased in both groups. Uropepsinogen excretion increased by 70% after protacine, and threefold after indomethacin (p less than 0.001). Occult blood search was positive in 1 patient receiving protacine, while 2 who were already positive before receiving protacine became negative during the treatment. Four patients taking indomethacin were found to be positive, 1 showing melaena. The one who was already positive before treatment showed increasing severity of occult bleeding during indomethacin administration. Frequency and severity of side-effects were significantly less with protacine (p = 0.004). In conclusion, protacine showed analgesic and anti-inflammatory actions significantly more potent and rapid than those of indomethacin, with significantly fewer and less severe side-effects.