OBJECTIVE: To examine whether insulin resistance and hypercholesterolaemia in obese Zucker rats are associated with a modification of the mechanical behaviour of a conductance (carotid) artery and with an altered endothelium-dependent response to acetylcholine of a small resistance (mesenteric) artery. DESIGN: Male obese Zucker rats, 6-8 months old, were compared with age-matched lean heterozygous and control Zucker rats. METHODS: The mechanical behaviour of the carotid artery was examined in anaesthetized rats by simultaneously monitoring the internal diameter with an A-mode ultrasonic echo-tracking device and the intra-arterial pressure with a computerized data-acquisition system. Furthermore, histometric measurements of the carotid artery were carried out after death. The response to acetylcholine was examined in vitro with a Mulvany dual myograph on precontracted isolated segments of the third-generation mesenteric artery. RESULTS: Obese Zucker rats exhibited high plasma insulin and cholesterol levels. Blood pressure was the same in the obese and control animals. There was no hypertrophy or change in the mechanical behaviour of the carotid arterial wall. Heart weight was slightly higher in the obese rats than in the controls, but smaller in relation to body weight. The relaxation to acetylcholine was significantly attenuated in isolated small mesenteric arteries obtained from the obese strain. CONCLUSION: Hyperinsulinaemia and hypercholesterolaemia in obese Zucker rats are associated with an abnormal response to acetylcholine in the mesenteric arterioles. This metabolic state does not, however, alter the mechanical behaviour or the geometry of the carotid artery.