A blood lipid-lipoprotein elevating effect of the diuretics hydrochlorothiazide and chlorthalidone in mildly hypertensive men has been established by a cross-over, randomized controlled trial, confirming previous clinical observations. Compared to baseline, plasma total cholesterol increased 6% and 8% and triglycerides 17% and 15% under treatment with hydrochlorothiazide and chlorthalidone, respectively. A cholesterol-lowering diet largely prevents this increase. Because these effects may be long-lasting and may cancel part of the potential benefit of blood pressure control in mildly hypertensive patients, with thiazide diuretics attention should be given to prescription of a cholesterol-lowering diet and to periodic monitoring of blood lipid levels. Different antihypertensive agents might be considered in patients with elevated blood lipid levels. Other antihypertensive agents currently in use need to be studied for potential effects on lipid metabolism.