The aim of this study was to investigate and compare the effects of two calcium antagonist drugs, verapamil (VER) and nifedipine (NIF), on blood pressure (BP), heart rate (HR), plasma catecholamines (pCA), renin (PRA), plasma aldosterone (pALD), and plasma volume (PV) in a group of patients with mild to moderate essential hypertension. In 12 hypertensive patients on a fixed normal sodium and potassium intake, VER (80 mg t.i.d., per os) first and then NIF (10 mg, t.i.d. per os), or vice versa according to a random sequence, were each given for 8 days, with an interval of 5 days between the two treatments. Both NIF and VER significantly reduced BP (p less than 0.001); this reduction was quantitatively similar in both treatment schedules. Supine and standing PRA, pALD, and PV were not significantly affected by VER or NIF. HR and pCA were unchanged after VER, whereas they were significantly increased (p less than 0.05, at least) mainly in standing position after NIF treatment. The antihypertensive and metabolic effects of VER (80 mg t.i.d.) and NIF (10 mg t.i.d.) were maintained after chronic treatment (4 months with VER in 10 patients and 2 months with NIF in 12 patients). After 2 months of treatment with VER (160 mg t.i.d.) in 18 patients, BP was further reduced, while pCA were slightly increased. In conclusion, VER and NIF are effective and equipotent antihypertensive agents that do not induce significant renin stimulation or fluid retention; adrenergic stimulation seems to be greater with NIF, which should be taken into account in the clinical use of these drugs.