We studied the effect of an ACE inhibitor (Enalapril [ENA], 10 mg o.d.) and a calcium-channel blocker (Nitrendipine [NIT], 20 mg o.d.) on insulin sensitivity in a double-blind cross-over study. Insulin sensitivity was measured by a two-step hyperinsulinemic euglycemic clamp. Serum potassium concentrations were kept constant during the clamp procedure by means of a variable potassium infusion. Twenty patients with essential hypertension (age 35+/-12 years [mean+/-SD], BMI 31.9+/-5.0 kg m2, initial blood pressure 152+/-10/99+/-6 mmHg) were treated with ENA or NIT for 4 weeks, respectively, with a wash-out period of 3 weeks. No carry-over effects or period effects were observed. Both drugs induced a comparable decline in systolic and diastolic blood pressure (ENA - 15+/-9/ - 13+/-8 mmHg, NIT -16+/-8/- 12+/-6 mmHg). No significant change in body weight occurred with both treatments (ENA -0.4+/-2.0; NIT 0.6+/-1.1 kg). Neither drug had a significant impact on any parameter of insulin sensitivity measured (e.g. insulin sensitivity index SI: ENA 5.2+/-2.0 [basal 5.1+/-2.2], NIT 5.8+/-3.0 [basal SI 5.1+/-2.4) mi/min x m2/microU/ml). In conclusion, no significant differences between ENA and NIT on insulin sensitivity were observed. The reduction of blood pressure had no apparent effect on insulin sensitivity.