The contractile response of the stomach fundus to endothelin-1 (ET-1) was examined in streptozotocin (STZ)-induced diabetic rats. In STZ-diabetic rats (versus age-matched control rats) (a) ET-1 caused a longer-lasting contraction of stomach fundus strips, and (b) in the dose-response curve, the ET-1-induced contraction was significantly greater for a given concentration (3 × 10^-7 to 10^-7 M). Although repeated application of ET-1 led to desensitization, the desensitization was less pronounced in STZ-diabetic rats than in the controls. The density of the binding sites for [¹²⁵I]-ET-1 was increased in the diabetic stomach fundus (versus the controls), but Kd values were similar between the two groups. The ET_B receptor mRNA expression level was significantly increased in the diabetic stomach fundus. These results suggest that the diabetes-related enhancement of the ET-1-induced contraction of the stomach fundus may be due to an increase in the ET_B receptor population.