The sympathetic nervous system (SNS) is an important regulator of the circulation. Its activity is increased in hypertension and heart failure and adversely affects prognosis. Although certain drugs inhibit SNS, dihydropyridine calcium antagonists may stimulate the system. Phenylalkylamine calcium antagonists such as verapamil have a different pharmacological profile. We therefore tested the hypothesis of whether amlodipine, nifedipine, or verapamil differs in the effects on muscle sympathetic nerve activity (MSA). Forty-three patients (31 men, 12 women) with mild to moderate hypertension were randomly assigned to 1 drug for 8 weeks. Blood pressure, heart rate, and MSA (by microneurography) were measured at baseline and after 8 weeks of treatment. All calcium antagonists led to a similar decrease in blood pressure of 5.0+/-1.5 to 6.4+/-1.4 mm Hg at 8 weeks (P<0.001 versus baseline). There were no significant differences in MSA between groups. With amlodipine, MSA averaged 49+/-3 bursts/min (3 versus baseline); with nifedipine, 48+/-3 bursts/min (2 versus baseline); and with verapamil, 49+/-2 bursts/min (all, P=NS). With verapamil, norepinephrine decreased by 4% but tended to increase by about one third with amlodipine or nifedipine (P=NS). Thus, in hypertension slow release forms of verapamil, nifedipine, and amlodipine exert comparable antihypertensive effects and do not change MSA, although there was a trend toward decreased MSA and plasma norepinephrine with verapamil.