Exchangeable sodium, blood volume, plasma norepinephrine, epinephrine, renin levels, and pressor responses to infused norepinephrine or angiotensin II were assessed in 10 patients with essential hypertension on placebo, following six to eight weeks of monotherapy with nifedipine, 3 X 10-20 mg/day, and after six to eight weeks on nifedipine combined with the diuretic chlorthalidone, 25 to 50 mg/day. Supine blood pressure was decreased after nifedipine alone (P less than 0.05) and even further after nifedipine + chlorthalidone (P less than 0.01). Body weight and exchangeable sodium increased after nifedipine (P less than 0.05), but were decreased after adding chlorthalidone. Blood volume was unchanged after nifedipine, but was reduced on nifedipine + chlorthalidone (P less than 0.05). Heart rate, supine plasma renin, catecholamine levels, and pressor responses to norepinephrine or angiotensin II were not consistently changed on nifedipine alone or combined with chlorthalidone. These findings indicate that in the established phase of treatment, nifedipine may exert its antihypertensive effect without necessarily altering cardiovascular responsiveness to norepinephrine and angiotensin II. Moreover, mild sodium retention may develop on nifedipine at least in some hypertensive patients.