Diuretics, when used for antihypertensive therapy, may also affect lipoprotein metabolism. The following observations were made after 1-12 months of treatment. Various thiazide-type diuretics significantly increased the potentially atherogenic serum low-density lipoprotein cholesterol (LDL-C) and/or very-LDL-C (V-LDL-C) fractions, while the antiatherogenic high-density lipoprotein cholesterol (HDL-C) level was largely unchanged. Certain loop diuretics also increased the LDL-C/HDL-C ratio. Both types of diuretics elevated serum triglyceride (Tg) levels in some, but not all, studies. Levels of LDL-C were increased in diuretic-treated men and in chlorthalidone-treated postmenopausal women, but not in chlorthalidone-treated premenopausal women. Only two diuretics evaluated, indapamide and spironolactone, had no apparent influence on lipoproteins. A tendency for increased Tg levels and lower HDL-C concentrations was apparent during combined thiazide-type diuretic-beta-blocker treatment; these changes resembled those observed during beta-blocker monotherapy. Diuretic-induced increases in LDL-C were prevented or reversed by concomitant beta-blockade, but not by combination treatment with sympatholytics such as reserpine, methyldopa, and clonidine. Prospective studies are needed to clarify the long-term course and the pathogenic and prognostic relevance of lipoprotein changes induced by various diuretics. In the meantime, it is of clinical interest that premenopausal women may be protected from thiazide-induced increases in LDL-C, certain diuretic agents have no significant effect on serum lipoproteins, and beta-blockers may prevent or reverse increases in LDL-C in men and postmenopausal women during diuretic treatment.