A double-blind, placebo-controlled, 4-week trial was performed to determine the antihypertensive and metabolic effects of enalapril (20 to 40 mg/d) in 16 hypertensive patients with non-insulin-dependent diabetes mellitus (NIDDM) aged 55 +/- 2 years and with a body mass index of 29 +/- 1 kg/m2. Glucose utilization was determined after an overnight fast and during insulin stimulation at 0 and 4 weeks (methods: euglycemic clamp, [3-3H]glucose infusion, indirect calorimetry). Enalapril decreased systolic (166 +/- 4 v 152 +/- 5 mm Hg, P < .05) and diastolic (102 +/- 2 v 95 +/- 2 mm Hg, P < .05) blood pressure. Peripheral insulin sensitivity, ie, insulin stimulation of glucose utilization, increased approximately 30%, or by 4.3 +/- 1.7 mumol/kg.min (13.1 +/- 2.0 v 17.4 +/- 3.5 mumol/kg.min, P < .05, 0 v 4 weeks) during enalapril treatment, but remained unchanged during placebo treatment (15.4 +/- 2.8 v 15.3 +/- 2.7 mumol/kg.min, respectively). The increase in glucose utilization during enalapril treatment was fully explained by an increase of 4.1 +/- 1.7 mumol/kg.min in glucose storage (4.1 +/- 1.2 v 8.1 +/- 2.9 mumol/kg.min, P < .05) while glucose oxidation remained unchanged. High-density lipoprotein (HDL) cholesterol increased by 8% (P < .05) and hemoglobin A1c (HbA1c) improved slightly (7.7% +/- 0.7% v 7.3% +/- 0.7%, P < .05) in the enalapril group, but not in the placebo group. We conclude that enalapril improves insulin sensitivity by increasing glucose storage in hypertensive patients with NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)