For treatment of unstable angina pectoris or recent myocardial infarction, intravenous NTG is frequently employed, beginning with doses of 3 mg/h or more; thereafter, dependent on the clinical course, in particular, if the blood pressure is lowered notably, the dose may be reduced to 1 or 2 mg/h. Reports published in recent years have documented to the development of tolerance to nitrates when given orally in higher doses three times daily or administered by the transdermal mode. Accordingly, we suspected that tolerance development would be the inevitable outcome during a continuous intravenous infusion of NTG. Consequently, this placebo-controlled study was undertaken to determine whether tolerance develops during a continuous 28-hour infusion of NTG and whether tolerance is reversible on interruption of the treatment with a twelve-hour infusion-free interval. The studies were performed in ten male patients ranging in age from 49 to 65 years, mean age 53 years. All patients had recovered from myocardial infarction (mean interval since infarction 42 days) and had reproducible, asymptomatic ST-segment depression of at least 0.2 mV during exercise testing after discontinuation of all antiischemic drugs with a washout period of three days. Exercise testing was performed at four hours after beginning the infusion of 1.5 mg/h NTG or placebo (2 p.m.), at 28 hours after beginning the infusion (2 p.m. on the second day) and, after having discontinued the infusion for a twelve-hour period (from 10 p.m. to 10 a.m.), at four hours after having re-started the infusion (2 p.m. on the third day).(ABSTRACT TRUNCATED AT 250 WORDS)