The role of T-lymphocyte subpopulations in the rejection of fetal pig proislet (islet precursor) xenografts in mice was examined with in vivo administration of monoclonal antibodies (MoAbs) to CD4+ (GK1.5) and CD8+ (49–11.1) T-lymphocyte subsets. The data indicate that the rejection process is T-lymphocyte dependent and mediated by CD4+ T-lymphocytes. The in vivo administration of MoAbs specific for graft-borne pig leukocytes failed to prevent xenog raft rejection in fully immunocompetent transplant recipients.