Transplant associated coronary disease (TxCAD) is the main cause of late graft loss following cardiac transplantation. It is a multifactorial disease with immunologic and nonimmunologic components involved. This study was undertaken to analyze the gene polymorphism in adhesion molecules in donors and recipients and to investigate its potential association with the development of TxCAD. A total of 82 cardiac transplant patients, 96 donors and 101 UK controls, were genotyped retrospectively. Nine nucleotide polymorphisms in L-selectin, E-selectin, ICAM-1, and PECAM were analyzed using allele-specific PCR-SSP assay. Recipients were selected on the basis of the development of TxCAD: patients who had developed TxCAD within 2 years after transplantation, and patients who did not have TxCAD within 4.5-5 years after transplantation. All recipients received CyA and azathioprine as a primary immunosuppression. Associations were assessed by using Fisher's exact test. No association was found between E-selectin, L-selectin, and PECAM allele or genotype frequencies and TxCAD. However, the donors whose recipients did not develop TxCAD at first 2 years had a significant increase of ICAM-1 E-469 allele compared with donors, whose recipients developed TxCAD (63.8% vs 46.4%, p = 0.042) and to UK controls (63.8% vs 47%, p = 0.04). Moreover, we found that the decreased frequency of ICAM E469 allele was associated with the increased number of rejection episodes. The 469 E/K polymorphism is in exon 6 and results in a change from glutamic acid to lysine in Ig-like domain 5 of ICAM-1, which is thought to affect interactions with LFA-1 and adhesion of B-cells. Our data suggest the presence of allele E469 ICAM-1 in either donor or recipient is protective against allograft rejection in a transplant setting.