Maximal treadmill exercise testing at 1, 3 and 8 hours was used to assess the onset, duration and antianginal efficacy of the dihydropyridine slow channel calcium-blocking agent, nisoldipine, in an oral dose range of 5, 10 and 20 mg. A double-blind, randomized, placebo-controlled design was used involving 12 patients with stable effort angina. Exercise tolerance was significantly increased 3 hours after each dose, when the maximal beneficial effect occurred. The improvement was observed as early as 1 hour after the 10 and 20 mg dose, and persisted for 8 hours after the 20 mg dose. At 3 hours, the onset of an exercise-induced ST segment depression of 0.1 mV or greater was increased by 62 (p less than 0.05), 75 (p less than 0.01) and 117 seconds (p less than 0.01) with the 5, 10 and 20 mg dose of nisoldipine, respectively, compared with placebo. Similarly, time to onset of angina was significantly increased. The sum of exercise-induced ST segment depression at peak exercise was significantly decreased (p less than 0.05) from 8.7 +/- 2.3 to 6.7 +/- 1.8 and 6.4 +/- 2.0 mm, respectively, after the 10 and 20 mg dose of nisoldipine. The rate-pressure product was significantly greater with nisoldipine than with placebo at the onset of ischemia and at peak exercise (22.8 +/- 1.1 versus 20 +/- 1.4 X 10(3) U for the 20 mg dose; p less than 0.01). Thus, nisoldipine is an effective antianginal agent with a rapid onset of action that improves exercise tolerance, increases angina threshold and persists for at least 8 hours after oral dosing.