Severe coronary artery spasm can occur in orthotopic cardiac transplant recipients. To investigate the possible mechanisms and relevance of coronary spasm to the subsequent development of coronary disease, the response of the coronary arteries to intracoronary ergonovine maleate was studied in 10 patients who had undergone orthotopic cardiac transplantation and were shown to have normal coronary arteries at angiography. Ergonovine in doses of 1, 5 and 10 micrograms was injected into the left coronary artery followed by 2 mg of isosorbide dinitrate. Proximal coronary artery luminal diameters were measured using automated computerized quantitative angiography of the left anterior descending (LAD) and circumflex (LCX) vessels. Five patients (responders) demonstrated a dose response curve to intracoronary ergonovine which was similar to that previously seen in non-transplant patients (mean percentage diameter change +/- SEM, -24.68 +/- 1.93 for LAD, -24.06 +/- 3.91 for LCX). The remaining five patients (non-responders) demonstrated a virtually flat dose response curve significantly different from that of the responders (P = 0.001 for LAD, P = 0.013 for LCX). Angiography after 2 years demonstrated significant coronary disease in four of the five responders to ergonovine. In contrast, the five non-responders to ergonovine continue to have no detectable disease by angiography.