Abnormalities in the serum lipid profile correlate strongly with the presence and severity of atherosclerosis. Increases in serum lipids and a reduction in high-density lipoprotein (HDL) cholesterol have been demonstrated following treatment with some beta blockers and diuretics, either alone or in combination. A new alpha-1-adrenoceptor antagonist, trimazosin, was studied to determine its effects on serum lipids. Ninety-six hypertensive patients were randomly assigned in double-blind fashion to trimazosin or placebo for 8 weeks. Trimazosin was associated with a significant reduction (p less than or equal to 0.01) in total cholesterol when compared with the placebo group. This effect was seen in all patients regardless of whether or not they were taking a diuretic concomitantly. In addition, a 9-month, double-blind parallel comparison was made of trimazosin and propranolol. Trimazosin was found to be superior to propranolol in its effect on HDL cholesterol and the HDL/total cholesterol ratio. These studies have demonstrated that, in contrast to placebo and propranolol, trimazosin lowers total serum cholesterol without undesirable effects on other serum lipid fractions. When polythiazide is given concomitantly, it diminishes the favorable effects of trimazosin and accentuates the opposite, adverse effects of propranolol.