Leukocyte binding to endothelial adhesion molecules has been said to be an initiating step in cardiac allograft rejection. Whether antibody blockage of leukocyte ligands, CD18, for intercellular adhesion molecule (ICAM-1) would prevent allograft rejection was studied in a rabbit heterotopic transplant model. Cervical cardiac transplant was performed between donor Staffland and New Zealand White recipient rabbits. Ten animals were treated with intravenous anti-CD8 monoclonal antibody, 60.3, at the dose of 1 mg/kg for 7 days. No immunosuppressive drugs were used. Eleven transplant controls were untreated. At 7 days, animals were sacrificed and donor heart histology was compared. Peripheral WBC counts were significantly higher in treatment group compared to untreated group on both postoperative day 2 and 7. The cellular rejection score was 30% lower in treated group than untreated (p < 0.05), demonstrating localization of lymphocytes to perivenular collections. The proportion of arteries with evidence of vasculitis was 45% lower in treated group. Results suggests that monoclonal antibody against LFA-1 (CD18) may hold promise as a therapeutic agent for both cellular and vascular rejection.