The antianginal efficacy and duration of action of slow-release (SR) diltiazem were evaluated in 12 patients with stable angina. Patients underwent maximal symptom limited bicycle exercise testing and 24-hour Holter monitoring at the end of 1-week placebo run-in phase and after 1-month therapy with either placebo or SR-diltiazem (120 mgs bid) using a placebo controlled, double-blind, randomized cross-over trial. No concomitant antianginal therapy, except sublingual nitroglycerin, was allowed during the trial. Exercise testing was performed 3 and 12 hours after drug administration. Blood samples were obtained for the determination of diltiazem plasma concentrations. After diltiazem administration, peak exercise duration increased significantly in comparison both with placebo and the run-in phase: from 292 +/- 48 to 378 +/- 113 s at 3 hours and from 286 +/- 59 to 366 +/- 109 s 12 hours after drug administration. Similarly, ST depression time increased from 240 +/- 59 to 374 +/- 123 s at 3 hours and from 231 +/- 57 to 332 +/- 123 s 12 hours after diltiazem. No significant changes of heart rate, blood pressure and double product were detected. Diltiazem plasma concentrations averaged, respectively, 175 +/- 86 pg/ml and 109 +/- 43 pg/ml 3 and 12 hours after its administration. No correlation was found between plasma concentrations and antianginal effects of diltiazem. At 24 hours Holter monitoring, SR-diltiazem induced a significant decrease of mean heart rate with a reduction in the number and duration of ischemic episodes.(ABSTRACT TRUNCATED AT 250 WORDS)