Amlodipine, a long-acting calcium antagonist, was compared with hydrochlorothiazide (HCTZ) in a long-term study of 139 patients. After a 2-week placebo run-in period, patients were randomly allocated to receive either amlodipine or HCTZ in a 2:1 patient ratio. After study week 12, those patients whose hypertension was not controlled with either monotherapy had atenolol added to their regimen. The daily dose range for amlodipine was 2.5-10.0 mg and for HCTZ was 25-100 mg. At study week 12, 24-h postdose blood pressure was reduced in both amlodipine (-16/-12 mm Hg supine; -14/-12 mm Hg standing) and HCTZ (-16/-11 mm Hg supine; -16/-10 mm Hg standing) groups. Response was defined as a supine diastolic blood pressure of less than 90 mm Hg or its decrease by greater than or equal to 10 mm Hg. Responder rates at the end of 12 weeks' monotherapy were 74.1% for amlodipine and 69.8% for HCTZ. Forty percent of patients randomized to amlodipine and 45% randomized to HCTZ achieved adequate blood pressure control ("response" as defined above) with monotherapy alone over the whole 50-week treatment period. The incidence of treatment-related side effects up to study week 12 was 46.7% with amlodipine monotherapy and 25.5% with HCTZ monotherapy. Two patients were discontinued from amlodipine and one from HCTZ for side effects during the first 12 weeks of the study, and a further four from amlodipine after week 12; none were discontinued from combination therapy.(ABSTRACT TRUNCATED AT 250 WORDS)