The main pharmacodynamic difference between angiotensin-converting enzyme-inhibitors (ACE-i) and angiotensin-II-receptor antagonists (All-r) is that ACE-i increase levels of bradykinin, which, in addition to vasodilation, may cause a decrease in insulin resistance. Hypertensive patients with diabetes type II suffering from side effects from ACE-i are frequently changed over to All-r. The objectives of this study were (1) to study whether this procedure reduces metabolic control, (2) to study effects on blood pressure and forearm blood flow (FLOW), and (3) to study possible associations between the variables hemoglobin A1e(HbA1e) and FLOW. A self-controlled sequential comparison is required to address such questions. Sixteen patients were treated with 10 mg enalapril or equipotent doses of other ACE-i for 6 months and subsequently with the All-r losartan at 50 mg daily for 6 more months. Patients were examined at the outpatient clinic every 4 to 8 weeks during the trial. FLOW was measured by iridium strain gauge venous occlusion plethysmography. Mean arterial pressure (MAP) increased by 4 ± 5 mm Hg (P<.05) after 6 months of losartan treatment as compared with the point of withdrawal of ACE-i. FLOW decreased by 5.4 ± 5.0 mL/100 mL tissue/min (P<.001), and HbA1eincreased by 0.6 ± 0.8 mmol/L (P<.05). Other metabolic variables, including cholesterol, high-density lipoprotein cholesterol, and triglycerides, were not significantly influenced by the change in therapy. Multiple regression analysis revealed that after adjustment for difference in HbA1e, the correlation between FLOW and MAP was unchanged, and after adjustment for difference in FLOW, the correlation between HbA1eand MAP was no longer significant. Replacement of ACE-i by All-r in hypertensive patients with type II diabetes mellitus induced a significant increase in HbA1eand MAP and a decrease in FLOW. The associations of HbA1eand FLOW with MAP were at least partly independent of each other, suggesting that mechanisms other than the bradykinin system (eg, the angiotensin2-receptor system) are involved. Our study design did not control for placebo and time effects, and so the data are of a preliminary nature.