The antihypertensive effects of isradipine and captopril were studied in 140 patients (70 men) with mild-to-moderate hypertension, aged 26 to 74 years, in a double-blind, randomized, between-patient comparative trial. Initial treatment started with 1.25 mg isradipine twice daily or 12.5 mg captopril twice daily. If normotension was not achieved after four weeks, doses were increased to 2.5 mg twice daily or 25 mg twice daily, respectively. If the maximum dose as monotherapy did not result in normotension, captopril (12.5 mg or, if necessary, 25 mg twice daily) was added to regimens of the isradipine-treated patients or isradipine (1.25 mg or, if necessary, 2.5 mg twice daily) was given in addition to the captopril-treated patients. After 24 weeks of active treatment, systolic blood pressure was significantly reduced (P less than .001) with isradipine (from 168 +/- 18 to 144 +/- 14 mm Hg) and with captopril (from 168 +/- 20 to 143 +/- 10 mm Hg). Diastolic blood pressure also fell significantly (P less than .001) in both groups (isradipine: from 105 +/- 5 to 84 +/- 5 mm Hg; captopril; from 105 +/- 4 to 85 +/- 4 mm Hg). With isradipine as monotherapy, diastolic blood pressure was normalized in 49% of patients compared with 56% with captopril as monotherapy (P = NS). Combining both drugs resulted in an increased rate of normalization (to 87%). The results indicate that combined treatment with a calcium antagonist and an angiotensin-converting enzyme inhibitor is effective in lowering blood pressure and is well tolerated during long-term therapy.