Unusual forms and causes of ischemic heart disease include angina pectoris in the presence of normal coronary arteries (syndrome X), congenital coronary abnormalities, vasculitic disorders, and graft atherosclerosis after cardiac transplantation. There is now evidence that endothelial dysfunction of coronary resistance vessels can account for abnormalities of the coronary microvasculature and possibly, myocardial ischemia and chest pain. The incidence of syndrome X appears to be higher in women, particularly those who have undergone hysterectomy. An intriguing hypothesis is that low estrogen levels may be associated with reduced expression of nitric oxide (reflecting endothelial dysfunction). The presence of coronary abnormalities in the young should not be underestimated. Syncope and arrhythmias are observed frequently in this patient population and warrant vigorous exploration. Worldwide, cardiac transplantation is now carried out in approximately 4500 patients yearly, with excellent (80% to 90%) 1-year survival due to improved immunosuppression. However, accelerated atherosclerosis develops rapidly postoperatively and is the main cause of late death. The link between cellular rejection of the myocardium and transplant coronary artery disease is not clear. The process of transplant coronary artery disease is believed to be due to chronic immune injury followed by intimal smooth-muscle proliferation and lipid deposition in the vascular wall. By the time it is detected by coronary angiography, the disease is far advanced and not susceptible to routine revascularization procedures. A prospective, randomized study of diltiazem versus no calcium blocker started early after transplantation has documented highly significant reductions in transplant atherosclerosis as measured by lumen narrowing, clinical events, and rates of retransplantation or death due to the process.(ABSTRACT TRUNCATED AT 250 WORDS)