OBJECTIVE To assess the effects of a vasodilatory beta-adrenoceptor blocker, nipradilol, and a long-acting Ca channel blocker, barnidipine, on insulin sensitivity. METHODS Insulin sensitivity was determined using a euglycemic hyperinsulinemic clamp technique before and after a 12-week treatment period in eighteen patients with essential hypertension. RESULTS Both drugs decreased blood pressure without affecting any serum parameters of glucose and lipid metabolism. Nipradilol significantly augmented glucose infusion rate (GIR) from 3.11+/-0.28 to 4.69+/-0.57mg/kg/min (p=0.027). Barnidipine also increased GIR from 3.91+/-0.43 to 5.29+/-0.43 mg/kg/min (p=0.028). Plasma norepinephrine concentrations significantly increased with barnidipine treatment, while nipradilol had no effect on plasma norepinephrine levels. No adverse events were reported during the study. CONCLUSIONS These results suggest that vasodilatory beta-blockers such as nipradilol and long-acting Ca channel blockers such as barnidipine may be useful in the treatment of insulin resistant hypertensive patients.