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Convenience of medicine-taking and lack of side effects are two major factors that favor compliance. Using a simple and convenient once-a-day regimen of minoxidil, nadolol, and chlorthalidone, we treated successfully 30 patients with moderate to severe hypertension. All patients were previously taking at least three medications, usually three to four times a day. Treatment was started with nadolol (160 mg) and chlorthalidone (50 mg) once daily. If diastolic blood pressure remained above 90 mmHg, minoxidil was added at a starting dose of 2.5 mg/day and increased weekly until blood pressure was controlled or the maximum dose of 100 mg/day was reached. The average blood pressure decreased from 170.9/107.0 mmHg (sitting) and 174.1/110.8 mmHg (standing), before the addition of minoxidil, to 138.8/86.7 mmHg (sitting) and 140.0/89.5 mmHg (standing), at the third month of minoxidil therapy. At the sixth month of minoxidil therapy, the figures were 140.9/86.3 and 141.9/89.8 mmHg. With this single-dose program, smooth blood pressure control throughout 24 hours was documented by 24-hour ambulatory blood-pressure monitoring. Hypertrichosis was common but was bothersome only to women patients. Pericardial effusions occurred in five patients, but they were all small and asymptomatic. Subjective side effects of the regimen were usually so mild that all patients who completed the study decided to remain on the same regimen.