Increases of triglycerides and total cholesterol have been reported during treatment with antihypertensive drugs, most notably with beta blockers and diuretics. ACE inhibitors, on the other hand, are not known for having a negative effect on lipid profile. To evaluate the effects of a fixed combination of captopril and hydrochlorothiazide on lipid metabolism, blood pressure, and quality of life, we performed an open prospective study. A total of 2,154 patients with or without hypercholesterolemia, but not receiving lipid lowering drugs, were enrolled. Of the 1891 evaluable patients at baseline, 34.1% had a moderate risk with total cholesterol between 5.2 and 6.5 mmol/l (mean 5.8 mmol/l) and 41.3% had a high coronary heart disease (CHD) risk with total cholesterol higher than 6.5 mmol/l (mean 7.3 mmol/l). After six months of treatment, the median cholesterol level in the moderate risk group decreased from 5.8 to 5.4 mmol/l (p less than 0.0003) and in the high risk group from 7.3 to 6.3 mmol/l (p less than 0.0001). Triglycerides also decreased, whereas high density lipoprotein (HDL) increased in both risk groups. Systolic and diastolic blood pressure fell as expected and quality of life improved. The fixed combination was well tolerated. We observed a significant improvement of lipid profile in patients with mild to moderate hypertension while undergoing treatment with the fixed combination of captopril and hydrochlorothiazide. We suggest that captopril may balance the negative effects of hydrochlorothiazide on lipid metabolism in patients with hypertension and concomitant hyperlipidemia.