alpha(1)-Adrenoceptor function and density in isolated thoracic aorta were measured during the course of streptozotocin-induced diabetes in rats. Diabetes was induced by a single tail vein injection of streptozotocin (60 mg/kg) and was verified by four measures (blood glucose level, increase in food intake, increase in water intake, and characteristic weight changes). Diabetes produced a significant increase in isolated aorta sensitivity to alpha(1)-adrenoceptor activation, manifested as a significant (p < 0.05) decrease in the A(50) value for phenylephrine and an increase in the A(50) (control)/A(50) (diabetic) ratio (1.2, 1.7, and 2.0, respectively) with increasing length of diabetes (4, 12 and 52 weeks). There was a large and biphasic change in receptor density (B(max)), without a significant change (p > 0.05) in either agonist (phenylephrine) or antagonist (prazosin) affinities (K(A) and pA(2) values, respectively). These results suggest compensatory mechanisms in receptor number and abnormalities in 2nd messenger transduction and can help direct efforts for improving antihypertensive or other pharmacological therapy for diabetic patients.