The effects of prazosin and beta-blocker monotherapy on serum concentrations of triglycerides, cholesterol, and lipoprotein cholesterol were evaluated in 16 patients with mild to moderate essential hypertension in a single-blind, cross-over, placebo-controlled study. Initially patients received a bid dose of either prazosin or a beta-blocker sufficient to maintain a sitting diastolic pressure below 95 mm Hg. After a placebo washout, patients were placed on the alternate medication. Fasting serum samples were obtained for lipid analysis during each treatment phase. Beta-blocker therapy was associated with undesirable changes in serum lipids as evidenced by increases in the concentration of total triglyceride (45%, P = .001), total cholesterol (4%, P = .05), LDL cholesterol (6%, P = .05) and VLDL cholesterol (21%, P = .05), and a decrease in the concentration of HDL cholesterol (-9%, P = .05). The ratios of total cholesterol to HDL cholesterol and LDL cholesterol to HDL cholesterol also increased by 15% (P = .005) and 18% (P = .005), respectively. No significant changes in any of the serum lipids were observed during prazosin administration.