Prazosin and propranolol were compared in an open, crossover study to determine their effects on plasma lipids and lipoproteins. After a four-week placebo period, 10 hypertensive patients were randomly assigned to prazosin treatment (Group I) and another 10 to propranolol treatment (Group II) for eight weeks. After a second four-week placebo period, treatment in each group was switched to the alternative drug for eight weeks. The mean blood pressure was reduced to normal levels (diastolic blood pressure less than or equal to 90 mm Hg) by both drugs--prazosin (1 to 8 mg per day) and propranolol (40 to 240 mg per day). The results of the study indicate that prazosin decreases serum cholesterol levels. In contrast, propranolol not only increases serum triglyceride levels and very-low-density lipoprotein cholesterol, but decreases total high-density lipoprotein cholesterol, high-density lipoprotein2 cholesterol, high-density lipoprotein2, and apoprotein A-I. The data suggest that propranolol may induce significant, potentially atherogenic changes in lipid metabolism, whereas prazosin may represent an advantageous alternative as an antihypertensive agent, especially in subjects with an already atherogenic lipoprotein profile.