Ketanserin, a selective S2 serotonergic antagonist, was assessed against placebo in a double-blind cross-over study of 16 patients with chronic peripheral burning pain. Nine of these had signs of reflex sympathetic dystrophy (RSD). All patients underwent 4 intravenous regional treatments, 2 with ketanserin (10 mg for upper limb pain, 20 mg for lower limb pain) and 2 with placebo. In those patients with RSD ketanserin and not placebo provided significant (P less than 0.05) sustained pain relief as assessed by linear analogue scales. In patients who did not fulfil the criteria for RSD no significant relief was seen with placebo or ketanserin. Following tourniquet release, drowsiness, shakiness and faintness were reported at a higher (P less than 0.05) frequency after ketanserin than after placebo. All side effects were mild and transient, and no changes occurred in heart rate or blood pressure following ketanserin that were significantly different from those seen following placebo. A role for serotonin in the pathogenesis of RSD is proposed.