We postulated that transplant coronary artery disease with rapid progression to more than 50% stenosis within a 1-year interval may have a different prognosis from transplant coronary artery disease with a more indolent rate of progression. Annual coronary angiograms of 139 consecutive patients who underwent transplantation between January 1968 and February 1990 who survived at least 1 year after transplantation and in whom angiographically apparent transplant coronary artery disease developed were included in the study. Of this group, 45 patients progressed from a normal angiogram to the presence of 50% or greater stenosis in one or more major vessels within 1 year (fulminant group); 94 did not (indolent group). Mean posttransplantation follow-up time was 5.3 +/- 4.1 years for patients with fulminant progression of disease and 6.6 +/- 3.7 years for those with indolent progression. A highly significant difference was found in the time-related incidence of ischemic events (myocardial infarction, congestive heart failure, sudden death, and retransplantation) between the indolent and the fulminant groups after initial detection of transplant coronary artery disease. At 1, 3, and 5 years after initial detection of transplant coronary artery disease, 50%, 33%, and 16% of patients in the fulminant group and 89%, 70%, and 60% of patients in the indolent group were free of ischemic events (p < 0.0001). The fulminant group of patients had a mean of 2.9 +/- 1.5 rejection episodes, and the indolent group a mean of 2.3 +/- 1.4 episodes (p = 0.02) during the first year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)