Diuretic drugs, when used in the treatment of hypertension, cause an increase in the serum concentration of total cholesterol and sometimes of triglyceride. High density lipoprotein (HDL) cholesterol remains stable with thiazide-type diuretic drugs. Treatment with furosemide, spironolactone, reserpine, and methyldopa does not affect serum total cholesterol or triglyceride concentrations. However, methyldopa decreases HDL cholesterol, and furosemide increases the ratio of total to HDL cholesterol. When reserpine, methvldopa, or beta-blocking drugs are added to diuretic therapy, triglyceride increases and HDL cholesterol decreases. The mechanism of the lipid-lipoprotein alterations is unknown, hut the changes correlate with changes in glycohemoglobin and serum glucose noted during diuretic-based therapy. The changes in total cholesterol and HDL cholesterol caused by some antihypertensive agents counterbalance the benefits on the development of coronary heart disease (CHD) expected from the control of blood pressure. Thus, treatment regimens with a more favorable influence on serum lipids may be crucial to better control of CHD. In the quest for such regimens, our data suggest that therapy which does not disturb glucose metabolism is likely to be free of lipid effect, and therefore, would quality as preferred therapy for hypertension