Effects of trapidil and nitroglycerin (glyceryl trinitrate) on coronary blood flow or epicardial coronary diameter were studied in conscious dogs, instrumented with a Doppler flow probe or a pair of ultrasonic dimension crystals on the left circumflex coronary artery. Bolus intravenous injections of trapidil (0.5, 1.0 and 2.0 mg/kg i.v.) increased coronary blood flow, dose-dependently, such being comparable at the peak value seen with nitroglycerin (5, 10 and 20 micrograms/kg i.v.). Coronary blood flow following the intravenous administration of trapidil or nitroglycerin increased biphasically and returned to pre-drug levels in 1.4 +/- 0.2 min (trapidil 1 mg/kg i.v.) or 1.0 +/- 0.1 min (nitroglycerin 10 micrograms/kg i.v.), while the mean coronary diameter increased monophasically and approached the control level 5 min after drug administration. The first peak was observed before the maximal decrease in aortic pressure and the second peak was associated with concomitant increases in heart rate and myocardial contractility induced by a sudden hypotension. Propranolol, a beta-blocker, did not modify the initial peak but attenuated markedly the second peak (P less than 0.05) in case of trapidil (1.0 mg/kg i.v.) or nitroglycerin (10 micrograms/kg i.v.), which corresponded with reduced changes in reflex tachycardia and positive inotropism. Therefore, the direct effects of trapidil and nitroglycerin on coronary circulation of conscious dogs are an initial transient dilatation of the resistance vessels followed by a continuation of the dilatation of the conductance coronary vessels.