&NA;We previously showed that intestinal tissue expression of lymphocyte function associated antigen‐1 is increased in animals with graft‐versus‐host disease after small‐bowel transplantation.HYPOTHESIS:Treatment of rats with monoclonal antibody to lymphocyte function associated antigen‐1 after small‐bowel transplantation will lessen the severity of graft‐versus‐host disease.METHODS:Graft‐versus‐host disease was created in Lewis X Brown‐Norway F1rats by heterotopic vascularized small‐bowel transplantation from Lewis donors. Transplanted rats were treated with either saline or various regimens of monoclonal antibody to lymphocyte function associated antigen‐1. Clinical characteristics, weight loss, spleen index, white blood cell counts, native intestinal histology, bowel permeability, and survival were then compared between groups and appropriate sham‐operated and lymphocyte function associated antigen‐1‐treated controls.RESULTS:Lymphocyte function associated antigen‐1‐treated rats lost less weight, had larger spleen indexes, more normal white blood cell counts, more normal native intestinal histology, less alteration in bowel permeability, and longer survival than untreated small‐bowel transplantation rats.CONCLUSIONS:In this model of graft‐versushost disease after small‐bowel transplantation, monoclonal antibody to lymphocyte function associated antigen‐1 treatment decreased the severity of graft‐versus‐host disease and prolonged rat survival.