Tolerance to arterial and venous effects is a common problem in longterm-therapy with nitrates when dosing schemes with multiple, regulary timed intervals throughout the day are applied. A balanced effect on preload and afterload is essential for a successful therapy of congestive heart failure. Interval therapy, the once daily medication of a nitrate, has a proven tolerancefree effect on preload. This study addresses the problem of afterload reduction under longterm interval therapy with nitrates. Nine patients with coronary heart disease NYHA II-III with congestion under exercise where included in the study. After a washout period they where treated with once-daily 120 mg ISDN s.r. Measuring mean arterial pressure and cardiac output, we compared the effect of the first dose (acute) with the effect after 5 weeks 1 x 1 120 mg ISDN s.r. (chronic). After acute therapy the mean arterial pressure under exercise was reduced by 14% from 121 +/- 12 mmHg to 104 +/- 11 mmHg. The average reduction of blood pressure under exercise was unchanged during chronic therapy (105 +/- 8 mmHg). Peripheral resistance was reduced by 21% from 914 +/- 266 to 722 +/- 190 dynsec/cm5 after the first dose. The afterload reduction was maintained during chronic therapy (727 +/- 176 dynsec/cm5).