The effect of 12-14 weeks streptozotocin-induced diabetes on contractile responses of the highly innervated caudal artery to adrenergic nerve stimulation was studied. The maximum contractile response and sensitivity (as reflected by the pD2 value) to noradrenaline (NA) was significantly greater in diabetic than in control caudal arteries. The maximum contractile response, but not sensitivity, to tyramine was significantly enhanced in diabetic compared with control caudal arteries when expressed as stress (mN/mm2), but not when expressed as a percentage of the maximum NA response obtained previously in the same tissues. No significant difference was detected between the responses of control and diabetic caudal arteries to electrical field stimulation of adrenergic nerves, when expressed either as stress or as a percentage of the corresponding NA response. Pretreatment with phentolamine markedly inhibited the contractile responses to field stimulation of both diabetic and control caudal arteries, while 6-hydroxydopamine essentially abolished responses to electrical field stimulation and tyramine in both tissues. Finally, pretreatment with hydrocortisone, timolol, and desipramine increased sensitivity to NA in control and diabetic caudal arteries by a similar magnitude. Thus, the enhanced contractile responses of caudal arteries from diabetic rats to NA do not appear to be associated with the development of autonomic neuropathy.