1. The effect of the intracoronary (i.c.) injection of 5-hydroxytryptamine (5-HT; 0.1-1.0 micrograms/kg) was examined before and after inhibition of nitric oxide (NO) synthesis with N-nitro-L-arginine (NOLA; 5 mg/kg i.c.) in nine anaesthetized greyhounds. Before administration of NOLA, 5-HT increased coronary blood flow (CBF) but decreased large coronary artery diameter indicating simultaneous dilatation of resistance vessels and constriction of large arteries. 2. The administration of NOLA significantly decreased large coronary artery diameter and increased systemic arterial pressure. There was no significant effect on coronary vascular resistance or heart rate. In the presence of NOLA, the 5-HT-induced constriction of the large coronary artery was enhanced and the dilatation of the resistance vessels was reduced. In addition there was a secondary reduction in CBF, a response that was not observed before NOLA treatment. 3. The response to NOLA suggests that a basal release of NO is important in the regulation of coronary and systemic vascular tone. Nitric oxide is an important mediator of coronary vasodilator responses to 5-HT, and in addition the release of NO modulates 5HT-induced constriction of large coronary arteries.