Earlier studies have shown that cardiovascular autonomic regulation is impaired in untreated or poorly controlled systemic hypertension. The purpose of this double-blind, randomized parallel trial was to evaluate whether improved blood pressure (BP) control can reverse this impairment. The study group consisted of 33 patients (age 45 to 63 years) with poor BP control who received randomized metoprolol or enalapril monotherapy. Baroreflex sensitivity (BRS) was assessed by phenylephrine test and time- and frequency-domain measurements of heart rate variability (HRV) were analyzed from 24-hour ambulatory electrocardiographic recordings during monotherapy and after 10 weeks of combination therapy with metoprolol + felodipine or enalaril + hydrochlorothiazide to lower casual BP to <140/90 mm Hg. Intensified treatment decreased 24-hour systolic and diastolic BP from 139 ± 12/86 ± 8 mm Hg to 126 ± 8/80 ± 7 mm Hg (p <0.0001). BRS improved from 6.2 ± 3.2 ms/mm Hg to 8.9 ± 4.1 ms/mm Hg (p <0.0001) and measurements of HRV (e.g., SD of all RR intervals from 128 ± 45 ms to 145 ± 46 ms, p <0.001) improved significantly during the combination therapy. Changes in BRS and HRV were similar in magnitude in both treatment arms. Mean RR intervals were comparable before and after intensive antihypertensive therapy (850 ± 124 ms vs 937 ± 279 ms, p = NS). These data indicate that adequate BP control with modern antihypertensive combination therapy can improve cardiovascular autonomic function, which may partially explain the reduced cardiac mortality observed in patients with intensified antihypertensive therapy.