Drug therapy for hypertension has failed to demonstrate a significant reduction in coronary mortality. We compared a calcium-antagonist agent, felodipine, with diuretic therapy as a first-line antihypertensive treatment in a randomized study, to assess the effects of six months of each regimen on over-all cardiovascular risk. Both regimens lowered blood pressure to less than 85 mmHg by one month. Felodipine alone was sufficient to control blood pressure in 90% of patients, while 50% of patients who were receiving diuretic therapy required a second agent for control. Diuretic therapy produced a 10% fall in serum potassium levels (P less than 0.001) and a three-fold increase in plasma renin activity (P less than 0.005) by one month; and a 6% rise in serum cholesterol levels (P less than 0.05) and a 38% rise in serum triglyceride levels (P less than 0.05) by three months. Felodipine did not influence these measurements, but caused a 43% increase in plasma noradrenaline levels by one month of therapy (P less than 0.025). In both groups, a significant fall occurred in the risk percentile score at six months, as calculated from the Multiple Risk Factor Intervention Trial data. However, the decrease was significantly greater in the felodipine group at six months (45% compared with 29%; P less than 0.05). Thus, when doses were titrated to achieve equivalent effects on blood pressure, felodipine had the advantages over diuretic treatment of being effective as monotherapy, of having fewer metabolic effects, and of reducing cardiovascular risk to a greater degree.