Although insulin resistance often occurs in association with hypertension, considerable variation is observed in the degree of insulin resistance among hypertensive patients. Since there is evidence of a genetic basis in the development of insulin resistance in hypertension, we analyzed the contribution of genetic factors to insulin resistance in hypertensive patients. Sixty-six Japanese hypertensive patients were studied. These patients were divided into two groups (hyperinsulinemia group and normoinsulinemia group) according to plasma insulin response during a 75-g oral glucose tolerance test (75g-OGTT). Insulin receptor gene (INSR) was studied for association with insulin resistance in hypertensive patients. A microsatellite polymorphism in intron-2 of the insulin receptor gene was analyzed by the polymerase chain reaction method. Five alleles were detected in the INSR microsatellite. The frequency of C/C genotype in the hyperinsulinemia group was significantly higher than that in the normoinsulinemia group (73% vs. 43%, p = 0.02). There was no difference in genotype frequency of INSR between hypertensive patients and control subjects. When the hypertensive patients were divided into two groups, the frequency of C/C genotype in the hyperinsulinemia group was significantly higher than that in the control group (73% vs. 45%, p = 0.014). There was no significant difference between the normoinsulinemia group and control group. These data suggest that the insulin receptor gene may contribute to insulin resistance in hypertensive patients with hyperinsulinemia.