In this study of the efficacy and safety of isradipine as first-line therapy in hypertension, 1,647 patients enrolled; 1,472 completed the 4-week placebo run-in period and began treatment with isradipine at 2.5 mg twice daily for 4 weeks. During placebo, 11% (n = 175) of the 1,647 patients withdrew because of normalization of blood pressure, side effects, noncompliance, violation of the study protocol, side effects from concomitant therapy, or other reasons. During isradipine therapy (n = 1,376), blood pressure decreased from 168 +/- 18/102 +/- 8 mm Hg at the end of the placebo period to 155 +/- 17/94 +/- 9 mm Hg after 2 weeks (p less than 0.001) and 151 +/- 16/92 +/- 9 mm Hg after 4 weeks (p less than 0.001). During active treatment, 6.4% (n = 94) were withdrawn because of flushing, headache, edema, palpitations, gastrointestinal side effects, skin rashes, or other side effects, and two patients because of lack of efficacy. The side effect score in the remaining patients worsened for flushing, remained unchanged for edema, but significantly improved for palpitations, fatigue, dizziness, headache, and nervousness. After 4 weeks, 60% of patients had diastolic blood pressures of less than or equal to 90 mm Hg. Thus, isradipine is effective and safe as first-line therapy in patients with primary hypertension as seen in general practice.