The efficacy and toleration of doxazosin and atenolol were compared over a 52-week period in a double-blind, multicenter study of 228 patients with mild-to-moderate hypertension. Over the treatment period, both drugs significantly reduced blood pressure, and there were no clinically or statistically significant differences between treatment groups for reductions in standing systolic and diastolic blood pressures or in sitting diastolic blood pressure. However, atenolol treatment caused significantly greater reductions in sitting systolic blood pressure and heart rate. Neither drug significantly affected total serum cholesterol concentrations. Doxazosin treatment lowered serum triglycerides, whereas atenolol treatment produced an increase in serum triglycerides (p less than 0.001, week 30; p less than 0.01, week 50, between treatment groups). Increases in high-density lipoprotein cholesterol and high-density lipoprotein to total cholesterol ratio were obtained with doxazosin treatment, whereas atenolol treatment decreased these lipid fractions (p less than 0.0001, weeks 30 and 50, between treatment groups). Using the Framingham equation, it was calculated that at week 50 the risk of developing coronary heart disease was reduced by 22% for the group taking doxazosin (p less than 0.001 vs baseline) and by 4% (not significant) for patients taking atenolol (p = 0.01, between treatment groups). It is concluded that doxazosin is a well-tolerated and effective antihypertensive drug with a favorable effect on blood lipids. Doxazosin provides an attractive, new alternative first-line drug for the treatment of mild-to-moderate hypertension.