Objective: Effective antihypertensive agents may differ in their capacity to reduce cardiovascular risk because they induce potentially atherogenic alterations in lipoprotein composition. Patients: To assess this possibility, the effects of five months' treatment with either hydrochlorothiazide (HCTZ) or the converting enzyme inhibitor captopril (CAPT) on lipoprotein lipid composition were compared in thirty normolipidaemic patients with essential hypertension (EH). Results: The sixteen patients treated with HCTZ showed the expected directional alterations in plasma TG (+ 31%), HDL2-C (-16%), and CHOL (+ 7.6%); in contrast TG and CHOL were unchanged after captopril in fourteen patients and their HDL2-C declined (-16%). Neither drug altered lipoprotein core lipid composition, but small increases were observed in the HDL2 sphingomyelin/lecithin ratio after both agents. The plasma free (unesterified) cholesterol (FC) lecithin (L) ratio, a new index of cardiovascular risk, was abnormally increased before treatment and was not altered by either drug. Conclusion: These findings indicate that HCTZ and CAPT treatment have small, but demonstrable effects on lipoprotein surface lipid composition in patients with EH that are confined to the HDL2 sub fraction.