Concern about the initial use of diuretic agents under the stepped-care approach to the treatment of hypertension has been voiced before. Recently, however, the level of concern has risen as the results of various trials have questioned the safety of these agents in mild hypertension. Diuretic-induced hypokalemia has been reported in 10 to 30% of patients on long-term treatment. Recent studies show that hypokalemia may lead to previously unsuspected and potentially fatal arrhythmias, particularly after infarction. Increases in plasma cholesterol of 10 to 20 mg/dl may occur with diuretic therapy. Diuretics are also known to decrease glucose tolerance. Beta-adrenergic blocking drugs, although useful in many situations, are contraindicated in about 25% of the hypertensive population. These agents may also pose a long-term atherogenic risk because of their adverse effect on lipid and glucose metabolism. If all these effects have the potential to increase the risk of coronary heart disease over the long term, then first-line administration of diuretic therapy and, to a lesser extent, beta-blocking therapy, to the 25 to 30 million Americans with diastolic pressure in the 90 to 100 mm Hg range must obviously be reassessed. Various alternative therapies, including withholding drugs for 6 months in patients with diastolic pressure of 90 to 100 mm Hg, using hygienic measures in patients not otherwise at high risk, and using other drugs such as the alpha 1-adrenergic inhibitor prazosin for initial therapy are discussed and evaluated.