The effects of untreated and insulin-treated streptozotocin-induced diabetes on the ability of the rat aorta maximally contracted with either 10(-4) M phenylephrine (PE) or 70 mM KCl to relax in response to 10(-5) to 10(-2) M theophylline (Theo) were examined. No significant differences between Theo-induced relaxation of the PE-contracture in control, untreated diabetic and insulin-treated diabetic aortas were observed until 12 weeks after the induction of diabetes. Twelve weeks after the induction of diabetes, the untreated diabetic aortas exhibited less relaxation in response to Theo than did the controls. This diabetes-induced decrease in relaxation of the PE-contracture was not reversed by insulin-treatment. Diabetes increased the ability of the K-contracted aortas to relax in response to Theo 4 weeks after the induction of diabetes. This diabetes-induced increase in the Theo-induced relaxation of the K-contracture was reversed by insulin-treatment. Even though there was no difference in the sensitivity of the PE-contracted tissues to Theo, the K-stimulated tissues from the untreated diabetic animals were more susceptible to the relaxing effects of Theo than either the control or insulin-treated aortas. These results indicate that diabetes affects the ability of the vascular smooth muscle to relax in response to theophylline, depending on the length of time in the diabetic state, the type of stimulus (PE or KCl) and whether or not insulin-treatment is applied.