The influence of hydrochlorothiazide and atenolol on serum lipoproteins was investigated in a randomized, prospective study on 68 men with essential hypertension. Cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDH) cholesterol, triglycerides, and the apolipoproteins AI and B were followed up to 42 months after starting therapy. Following atenolol serum (HDL) cholesterol decreased and serum triglycerides increased significantly (p less than 0.01) from 6 to 42 months. After hydrochlorothiazide serum triglycerides, LDL cholesterol and total cholesterol all increased significantly (p less than 0.01) from 12 to 42 months. The changes were more pronounced under higher doses with beta blockade, but not with diuretics. Thus, both atenolol and hydrochlorothiazide have adverse but different effects on serum lipoproteins after long-term administration. Continuing investigation is necessary to determine whether these side effects decrease the benefit of blood pressure reduction in patients with hypertension.