1. The effect of treatment with a thiazide-like diuretic alone or combined with a β-adrenoceptor blocker on serum lipoproteins was investigated in 35 patients with essential hypertension. 2. In group I (18 patients), serum low-density lipoprotein cholesterol was increased (P < 0.001) during monotherapy with chlorthalidone (100 mg/day) but not during combined chlorthalidone-β-blocker therapy. 3. This tendency was similar in subgroups studied with an inverse sequence of drug administration. In subgroup IA (11 men), a 22% increase (P < 0.01) in low-density lipoprotein cholesterol after 6 weeks of chlorthalidone was reversed after use of a β-blocker as well as chlorthalidone; in subgroup IB (five men, two post-menopausal women), low-density lipoprotein cholesterol was increased by 41% (P < 0.05) above placebo values 6 weeks after withdrawal of the β-blocker from combination therapy. 4. In group II (18 men), low-density lipoprotein cholesterol was increased by 13% (P < 0.025) after 4 weeks of monotherapy with clopamide (5 mg/day) but restored to control levels 4 weeks after addition of pindolol (10 mg/day). 5. No significant changes occurred during any treatment phase in high-density lipoprotein cholesterol. 6. Certain β-receptor blocking agents may prevent or reverse diuretic-induced increases in serum low-density lipoprotein cholesterol.