In this double-blind cross-over study 16 patients with mild-to-moderate hypertension were treated with placebo and the dihydropyridine derivative, isradipine 5-10 mg twice daily. In the supine position isradipine reduced systolic (-18 mm Hg; p less than 0.002) and diastolic (-15 mm Hg; p less than 0.001) pressures, while heart rate was not changed; in the standing position, systolic (-15 mm Hg; p less than 0.002) and diastolic (-14 mm Hg; p less than 0.001) pressures decreased, whereas heart rate increased (+6 bpm; p less than 0.05). Body weight and lower leg volumes remained unaltered, suggesting that isradipine did not cause fluid retention. On IS plasma angiotensin I (+40 pg/ml), angiotensin II (+ 14 pg/ml), and aldosterone (+4.1 ng/dl) rose. The intracellular Na+ and K+ concentrations and the transmembrane cation transport activities (Na+-K+ pump, Na+-K+ cotransport, Na+-Li+ countertransport), measured ex vivo in the erythrocytes of eight male patients, were not significantly influenced by isradipine. Hot flushes and facial erythema occurred more frequently (p less than 0.05) on isradipine than on placebo. In conclusion, the new calcium entry blocker isradipine at a dose of 5-10 mg twice daily lowers blood pressure and is well tolerated in most patients with essential hypertension.