Certain dynamics of rejection after heart transplantation can be characterized by measuring soluble interleukin-2 receptor levels. To determine whether elevated levels could predict development of coronary artery disease, the mean of three weekly determinations the first month after heart transplantation, as well as values obtained at 6 months, 12 months, 18 months, and 24 months after the procedure, were evaluated. Comparison was made between the groups in whom allograft arteriopathy did or did not develop. Concomitant endomyocardial biopsy scores also were evaluated. Fifty-five patients surviving the initial 30 days after heart transplantation were prospectively followed up. Eighty-five percent were male, and the median age was 51 years. Coronary arteriopathy developed in 15 patients (27%) during a mean follow-up period of 26 months (range, 1 to 54 months). For the early follow-up point, mean (+/- standard deviation) receptor levels for those patients without allograft arteriopathy were 880 +/- 846 U/ml and for those with arteriopathy, 1410 +/- 590 U/ml (p = 0.001). At each follow-up point thereafter, soluble interleukin-2 receptor levels were greater in the group with allograft arteriopathy. Indeed, at all observation points, the group in whom disease developed had levels greater than 1000 U/ml, and these values were, from a statistical standpoint, always greater than the group without detectable arteriopathy. In contradistinction, endomyocardial biopsy scores were no different at either early or late follow-up periods. Allograft arteriopathy after heart transplantation seems predicted by early elevation of plasma soluble interleukin-2 receptor levels, and patients with this difficulty generally have elevated levels during long-term follow-up.