Rejection dynamics after heart transplantation might be characterized by soluble interleukin-2 receptor levels. To determine whether elevated levels early (measured by enzyme-linked immunosorbent assay once weekly the first 3 weeks at time of heart biopsy) after transplantation predict mortality and development of coronary disease, the means of these three determinations and the endomyocardial biopsy scores (McAllister scale 0-10) were compared for survivors and nonsurvivors and patients who had coronary arteriopathy develop and those who did not. Fifty-five patients alive 30 days after heart transplantation were prospectively followed up. Overall, 47 patients were male (85%), and the median age was 51 years. Mean +/- SD follow-up was 26 +/- 15 months (range, 1 to 54 months). There were 38 survivors (69%), and coronary arteriopathy developed in 15 patients (27%). Whereas mean +/- SD heart biopsy scores for the early weeks were similar between survivors and nonsurvivors (3.6 +/- 1.4 vs 4.4 +/- 1.6; p greater than 0.05), the difference in soluble interleukin-2 receptor levels was significant (703 +/- 362 U/ml vs 1793 +/- 1070 U/ml; p less than 0.001). A mean level less than 1000 U/ml in any given patient predicted long-term survival with a 76% sensitivity, 79% specificity, and 88% negative predictive value. Mean receptor levels for those patients in whom coronary arteriopathy did not develop were 880 +/- 846 U/ml and for those with this difficulty, 1410 +/- 590 U/ml (p = 0.001). Late morbidity and mortality after heart transplantation seem predicted by early elevation of plasma soluble interleukin-2 receptor levels.(ABSTRACT TRUNCATED AT 250 WORDS)