This study evaluates the vasoactive effects and mode of action of ketanserin, a selective 5HT2 receptor antagonist, on digital circulation in 11 patients with primary Raynaud's phenomenon. Reflex digital vasoconstriction was induced by moderate body cooling. We found that ketanserin given intravenously in a dose of 10 mg, normalized digital skin temperature and digital blood flow as estimated by venous occlusion plethysmography and laser-Doppler flowmetry. However, effects of ketanserin on transcutaneously measured oxygen pressure were modest. This could imply a preferential effect of ketanserin on arteriovenous shunt flow. Pretreatment with high doses of the selective and nonselective alpha-adrenoreceptor antagonists prazosin and phentolamine did not abolish the effects of ketanserin on digital blood flow. However, under alpha-adrenoceptor blockade the small effects of ketanserin on normal blood pressure disappeared. Thus, in contrast to the effects in the systemic circulation, the principal mechanism underlying digital vasodilation after ketanserin is unlikely to involve alpha-adrenoceptor antagonism. We conclude that 5HT2 receptors are present in the digital vasculature. In patients with primary Raynaud's phenomenon, their activation plays an important role in cold-induced digital vasoconstriction.