The efficacy of the 5-HT-2-receptor antagonist, ketanserin, in the treatment of Raynaud's phenomenon was assessed in a double-blind, placebo-controlled, crossover trial in nine patients with generalized scleroderma (GS). Each patient received ketanserin 20 mg or placebo three times a day in the 1st week and 40 mg ketanserin or placebo three times a day for the remaining 4 weeks, and was then crossed over for 5 weeks. Measurements were made of finger blood pressure and flow during a cold challenge test and patients recorded numbers of Raynaud's attacks. No significant improvement was found in reactions to cold provocation or in numbers of Raynaud's attacks during ketanserin treatment, but intolerable side-effects were common. Interactions with concomitant medication might be a possible explanation for this. We conclude that ketanserin in the dose given, is not effective in the treatment of Raynaud's phenomenon in GS.