The vascular responses of isolated and perfused atherosclerotic rabbit common carotid arteries to 5-HT were investigated. Atherosclerotic lesions were produced by positioning a hollow silicone collar around the common carotid arteries of rabbits fed with an atherogenic diet for 4 weeks. After the period, we removed the vessels from operated and sham-operated rabbits fed with either the atherogenic diet or a normal diet for 4 weeks. The removed vessels were divided into four groups: a control group, a cuffed normal-diet-fed group, a sham-operated, cholesterol fed group, and a cuffed cholesterol-fed group. Vascular effects of 5-HT and its analogs (5-CT, a 5-HT1-like receptor agonist; alpha-methyl-5-HT, a 5-HT2 agonist; 8-OH-DPAT and TFMPP, 5-HT1 agonists) were investigated in each group. The vasoconstrictor responses to 5-HT, 5-CT and alpha-methyl-5-HT were enhanced in atherosclerotic vessels. Removal of the endothelium did not affect the vascular responses to 5-HT and its analogs. Because the responses were not enhanced in vessel from a cuffed normal-diet-fed group, we did not show the data of this group in figures and did not examine antagonism studies. Vasoconstrictor responses to these agonists were markedly inhibited in other three groups by ketanserin and spiperone (5-HT2 receptor antagonists), and methysergide (a 5-HT1 and 5-HT2 receptor antagonist). 5-HT and its analogs did not show any vasodilatory action on phenylephrine-preconstricted preparations, which suggested that there were few functional 5-HT1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)