No single pathophysiologic mechanism explains adequately cold-induced vasospasm in all forms of Raynaud's phenomenon. Local serotonin release from activated platelet is a contributory element in those disorders typified by structural arterial change. e.g., systemic sclerosis (seleroderma) Selective antagonism of S2 serotonergic receptors with ketanserin improves both maximal digital artery flow and cold tolerance. Platelet-derived growth factors, and serotonin itself may contribute to the fibrotic arteriosclerosis of this disorder. In contrast, in primary (spastic) Raynaud's phenomenon, ketanserin relieves but does not prevent cold-induced vasospasm, which suggests that the role of serotonin is in maintenance of but not provocation of an attack. Antiplatelet therapies could benefit both disorders.