Splenic tissue from mice was autotransplanted; after initial necrosis, a rapid restoration of implants into a structure histologically indistinguishable from splenic tissue was observed. The development of the marginal zone in these autotransplants, as determined with monoclonal antibodies against different splenic cell types and routine histological stains, was compared with the local and systemic response against a thymus-independent (TI) type 2 antigen. Full restoration of time course and peak of anti-trinitrophenyl (TNP) serum titres against TNP-Ficoll was observed at 4 weeks after autotransplantation. Anti-TNP antibody-forming cells were observed in subnormal and normal numbers in 2- and 4-week old autotransplants, respectively. The appearance of normal numbers of antibody-forming cells, and the restoration of antibody titres at week 4 correlated with the return of newly formed B cells in a normal marginal zone. An unexpected observation was that marginal zone macrophages did not return until 10 weeks after transplantation, thereby making the necessity for these cells in the normal TI-2 response unlikely. We conclude that normal anti-TI-2 responses (onset and peak titres) can be restored by autotransplantation of splenic tissue. B cells and marginal zone organization are responsible for this response, for which marginal zone macrophages seem expendable. The partial protection against overwhelming post-splenectomy infections, given by autotransplants, can thus be explained by restorative capabilities of these implants on antigen presentation and antibody formation against TI-2 antigens, and not by an increase (compared with splenectomized individuals) of phagocytosis by marginal zone macrophages.