Anti-LFA-1 monoclonal antibodies (mAb) prolong graft survival in several animal models. This study assessed the effect of an anti-LFA-1 mAb (WT.1) on small bowel allograft rejection, circulating leukocyte subsets and in vivo target cell antigen blockade. Heterotopic small bowel transplantation was performed between PVG donor and DA recipient rats. Transplanted animals received 1 mg/kg per day WT.1 on days -1, 0 (day of transplantation) and 1. Three doses of WT.1 were also administered to a group of untransplanted animals to monitor circulating leukocyte populations and in vivo binding. WT.1 prolonged recipient survival from 7 to 14 days. Peripheral leukocyte counts increased more than twofold, primarily due to marked increases in both CD4+ and CD8+ lymphocytes. Approximately 85% of WT.1 binding sites on lymphocytes and monocytes were blocked/modulated after the course of therapy. WT.1 has marked effects on circulating leukocytes and target cell binding capacities and can affect the survival of rat small bowel transplant recipients.