Cardiac allograft arteriosclerosis limits long-term survival of recipients and is characterized by intimal thickening comprised of proliferative smooth muscle cells. Proliferating-cell nuclear antigen (PCNA) plays a pivotal role in the cell cycle regulatory genes involved in smooth muscle cell proliferation. To test the hypothesis that antisense PCNA oligodeoxynucleotide (ODN) can prevent allograft arterial intimal hyperplasia, we performed single intraluminal delivery of the antisense or sense PCNA ODN or no transfer into murine cardiac allografts. DBA/2 murine hearts were transfected and transplanted into B10.D2 mice; the allografts were harvested 4 weeks later. Severe intimal thickening with enhanced expression of PCNA was observed in untransfected and sense PCNA ODN-treated allografts, whereas antisense PCNA ODN prevented neointimal formation.