1. Antihypertensive treatment has been demonstrated to result in persistent reductions in morbidity and mortality due to stroke. However, the coronary risk attributable to hypertension has been only partially reversed. We hypothesized that diuretics could have unfavourable effects on atherosclerosis. 2. New Zealand rabbits were fed a 0.5% cholesterol-enriched diet for 12 weeks, followed by a 0.1% cholesterol diet for another 12 weeks. During the last 12 week period, 40 animals were randomly assigned to one of four groups: (i) group I was the control group; (ii) group II received hydrochlorothiazide (10 mg/day); (iii) group III received quinapril (30 mg/day); and (iv) group IV was treated with hydrochlorothiazide (10 mg/day) plus quinapril (30 mg/day). 3. The treatments did not affect either the lipid profile or serum electrolytes and oxidative stress. However, endothelium-dependent vasorelaxation in isolated aortic rings was significantly improved with quinapril (group III) treatment (P < 0.001 vs other groups). In addition, therapy with quinapril promoted a significant reduction in atherosclerosis (intima area, intima/media ratio and perimeter of vessel with plaque; P < 0.05 vs other groups), as well as in cholesterol content of the aorta (P < 0.05 vs groups II and IV). 4. In conclusion, hydrochlorothiazide did not modify atherosclerosis and, when added to quinapril treatment, impaired the anti-atherosclerotic effect seen with quinapril alone.