A novel therapy for rheumatoid arthritis, regional sympathetic blockade using guanethidine, was investigated in 24 patients with active disease. In a randomized double blind short-term (14 days) study, we evaluated the effect of therapy on subjective responses, change in pain, stiffness, and morning stiffness and no objective responses, change in pinch strength, grip strength, and joint tenderness. Compared to placebo, guanethidine produced a decrease in pain (p less than 0.025) and an increase in pinch strength (less than 0.025) over the 2-week duration of the study. The therapeutic effect of guanethidine may be mediated by an interruption of the proinflammatory effects of the sympathetic nervous system.