Bepridil, a new calcium-channel blocking agent with an extended plasma elimination half-life of greater than 50 hours, was compared to placebo in 77 patients with confirmed coronary artery disease and chronic stable angina pectoris. The effects of bepridil were compared with those of placebo on angina frequency, nitroglycerin tablet use, the resting ECG and hemodynamics at rest and maximal exercise using a study design comprising 5 sequential 2-week single-blind treatment phases. After 2 weeks of placebo (phase 1), bepridil was given for 3 phases (2, 3 and 4) at total daily dosages of 200, 300 and 400 mg, respectively; the study was completed after a final reintroduction of placebo (phase 5). Within each phase once- and twice-daily regimens of bepridil were randomly compared. Bepridil (300 mg/day) reduced anginal frequency 68%, from 8.5 +/- 1.1 (standard error of the mean) to 2.7 +/- 0.7 attacks/week and nitroglycerin tablet use 76% (p less than 0.001). Bepridil improved exercise duration 26%, from 6.9 +/- 0.4 to 8.7 +/- 0.5 minutes (p less than 0.001) and exercise work 52%, from 2.7 +/- 0.3 to 4.1 +/- 0.4 kpm X 10(-3) (p less than 0.001) on a standardized treadmill protocol. Resting and peak exercise heart rate and blood pressure were unaffected by bepridil. The antianginal effects were similar with either once- or twice-daily treatment schedules. Minor side effects of nausea, epigastric discomfort and tremor were infrequent and there were no major side effects. The results of this large but preliminary, single-blind and short-term study suggest that bepridil is an effective and well tolerated antianginal agent when administered once daily.