The effectiveness of dothiepin (a tricyclic anti-depressant) at a dose of 75 mg given orally at night was compared with placebo for 4 weeks in alleviating pain in 60 patients with classical or definite active rheumatoid arthritis. Patients were classified as either 'depressed' or 'not depressed'. The week before, during and 2 weeks after the study, 600 mg ibuprofen was given orally three times daily to all patients. Compared with placebo, dothiepin produced a significant reduction in daytime pain by the end of the treatment period. The Hamilton rating scale in 'depressed' patients was significantly improved in patients given dothiepin. The Cassano-Castrogiovanni self-evaluation rating scale in both 'depressed' and 'not depressed' patients showed a tendency (not significant) to be improved following dothiepin treatment compared with placebo. These results suggest that patients with rheumatoid arthritis may experience an increase in pain symptoms due to an alteration of mood. Therapy with tricyclic anti-depressants, such as dothiepin, therefore, may determine an improvement of pain indexes besides having an anti-depressant effect.