Neonatal splenectomy and congenital absence of the spleen were shown to be associated with lack of primary IgM antibody synthesis, deficient bone marrow-thymus cell synergism. altered mitogen responsiveness and depressed homing patterns of thymocytes to the spleen. Using congenitally asplenic animals, altered B-T cell cooperation was manifest at the T cell but not B cell level. This correlated with the ability of thymus cells from either congenitally asplenic or neonatally splenectomized (NSx) animals to respond to the B cell mitogen lipopolysaccharide although there were no detectable Ig=ells present. To determine the role played by the spleen in the development of T cell function, NSx animals were given either irradiated or normal spleen grafts. Both irradiated and unirradiated grafts restored normal B-T cooperation and normal mitogenic responses of thymus cells. However, neither type of spleen graft was successful in restoring normal homing patterns to the spleen. It is concluded that the splenic microenvironment influences T cell maturation very early in life and that only some of the effects attributable to the absence of the spleen can be reversed by the reintroduction of this tissue as a graft.