In short-term studies (4 to 6 months) we have reported that antihypertensive treatment with beta-adrenergic blockade and thiazide diuretics induced insulin resistance, hyperinsulinemia, and a deranged lipid profile; the ACE inhibitor captopril increased insulin sensitivity without affecting serum lipids. In the present study, 65 of the original 149 patients with essential hypertension included in the short-term studies were reexamined after treatment for 2 to 3 years. The hyperinsulinemic euglycemic clamp method showed that the significant decrease in insulin sensitivity (p < 0.01) induced by treatment with pindolol, propanolol, metoprolol, atenolol, or hydrochlorothiazide after 4 to 6 months persisted after 2 to 3 years of treatment. Furthermore, the increase in insulin sensitivity reported for captopril after 6 months (p < 0.05) was not significantly altered during long-term treatment. Also, the raised levels of very low-density lipoprotein triglycerides (p < 0.01) and reduced levels of high-density lipoprotein cholesterol (p < 0.01) induced by most of the beta-adrenergic blockade without intrinsic sympathomimetic activity and hydrochlorothiazide persisted. Captopril, on the other hand, did not significantly affect the lipids during prolonged treatment. In conclusion, the magnitude of the metabolic effects induced by antihypertensive treatment during short-term studies was of the same order after long-term treatment over 2 to 3 years and were not significantly different from the results in the short-term studies.