The efficacy of nicardipine, a new calcium ion antagonist, was studied in 39 patients aged 42 to 70 years with chronic stable angina in two different placebo-controlled single- and double-blind crossover trials and with long-term follow-up, using serial quantitated exercise testing and ambulatory ST segment monitoring. In the first study the minimal effective dose was determined, and in the repeat study the effects of three different dose levels were evaluated. Treadmill exercise testing was performed at the end of each 2 week treatment period with on-line computer analysis of the electrocardiogram. The mean (+/- standard error of the mean) exercise time was 6.8 +/- 0.7 minutes on placebo and 7.0 +/- 0.8 minutes during treatment with nicardipine, 60 mg/day (p = NS). This increased to 8.7 +/- 0.8 (p less than 0.001) and 9.2 +/- 0.9 minutes (p less than 0.001) with 90 and 120 mg/day, respectively. The mean heart rate at rest during placebo administration was 75 +/- 2 beats/min and increased to 85 +/- 3, 84 +/- 2 and 88 +/- 3 beats/min (p less than 0.02, p less than 0.01, p less than 0.01, respectively) at each dose level. The time taken to develop 1 mm of ST segment depression was prolonged from 4.8 +/- 0.6 minutes during placebo administration to 5.3 +/- 0.7 (p = NS), 6.4 +/- 0.7 (p less than 0.01) and 6.7 +/- 0.8 minutes (p less than 0.001), respectively, at each dose level. The improvement achieved after 2 weeks of nicardipine, 120 mg daily, was maintained over a period of 6 months of follow-up. Three patients were withdrawn, one taking 60 mg of nicardipine, one taking 90 mg of nicardipine and one taking placebo, but the overall incidence of side effects was low. Nicardipine is an effective antianginal agent with an optimal dose of 90 to 120 mg/day.