Thirty-three men with stable exercise-induced angina pectoris entered a randomized, double-blind, crossover study in which controlled-release isosorbide-5-mononitrate 60 mg once daily was compared with conventional isosorbide dinitrate 20 mg 3 times daily. Each drug was given for 2 weeks. Twenty-eight patients completed the study and data on exercise variables are available in 23 patients. Treatment with either drug resulted in significant antianginal effects, when measured 6 hours after a single dose and after 2 weeks of therapy compared with baseline placebo; however, there were significantly fewer signs of myocardial ischemia during treatment with isosorbide-5-mononitrate. There was no evidence of tolerance to either drug treatment but a significant attenuation of resting blood pressure (but not of exercise blood pressure) was observed with both drugs. Headache was the only clinically significant adverse event during therapy and it occurred more frequently in the isosorbide dinitrate treatment group (p less than 0.05 vs placebo); 3 such patients had to withdraw from the study because of headache. Thus, once-daily, controlled-release isosorbide-5-mononitrate appears as effective as conventional isosorbide dinitrate 3 times daily in patients with stable angina pectoris. The once-daily administration is convenient and improves patient compliance.