5-Hydroxytryptamine has been suggested to be a mediator in peripheral cold-induced vasospasm. In order to investigate the contribution of different 5-hydroxytryptamine receptor subtypes in the contractile response during cooling, segments of subcutaneous hand veins obtained from 50 patients undergoing hand surgery were examined in vitro in organ baths. The temperature in the bath was initially 37 degrees C and was either continuously lowered to 10 degrees C or kept constant at 37 degrees C, 29 degrees C. Cooling to 25 degrees C augmented the contractile response to 5-hydroxytryptamine in intact as well as in endothelium-denuded segments. The 5-hydroxytryptamine2 receptor antagonist ketanserin antagonized the contractile response to 5-hydroxytryptamine at 37 degrees C, and in addition abolished the cold-induced enhancement of the response during cooling. This points to a major role of the 5-hydroxytryptamine2 receptor in the cold-induced augmentation of the response to 5-hydroxytryptamine, which was further supported by increased contractions to the 5-hydroxytryptamine2 receptor agonist alpha-methyl-5-hydroxytryptamine during cooling. Contractile responses were also obtained by the selective 5-hydroxytryptamine1-like receptor agonist GR43175 interpreted to indicate the presence of a smaller 5-hydroxytryptamine1-like receptor population. However, the response to GR43175 was unaffected by cooling. These results warrant further investigations of the role of 5-hydroxytryptamine in cold-induced peripheral vasospasm.