The effects of the angiotensin-converting enzyme inhibitor trandolapril on blood pressure, insulin sensitivity, and other metabolic variables were assessed in this open study of 45 patients (27 women and 18 men; mean age, 53.1 ± 14.0 years; mean body weight, 83.4 ± 12.4 kg) with hypertension (blood pressure >140/90 mm Hg). Fasting and postprandial serum insulin and plasma glucose concentrations were measured daily before and after trandolapril administration (2 to 4 mg/d) for 12 weeks. Systolic and diastolic blood pressures and low-density lipoprotein cholesterol concentration were reduced significantly. Mean fasting insulin concentrations fell from 56.4 ± 38.0 pmol/L to 42.4 ± 28.0 pmol/L, and during an oral glucose tolerance test (OGTT) from 341.6 ± 305.0 pmol/L to 242.7 ± 229.0 pmol/L at 2 hours. The ratio of mean fasting insulin to glucose fell from 0.7 ± 0.4 to 0.5 ± 0.4, and during OGTT the ratio fell from 3.3 ± 2.0 to 2.6 ± 1.7 between 1 and 2 hours. Total cholesterol decreased and high-density lipoprotein cholesterol increased, although neither change was significant. After trandolapril treatment, insulin and glucose concentrations improved. The lack of negative effects of trandolapril on metabolic variables may offer advantages not seen with other anti-hypertensive agents such as beta-blockers and diuretics.