In mice lacking the src family protein tyrosine kinase, p 56lck (lck -/-), a greatly reduced number of peripheral T cells is observed due to a profound blockage of the thymocyte development. The peripheral T cells in lck -/- mice exhibit proliferative response after T-cell receptor (TCR)-crosslinking, but can not respond to viral antigens. In this report, we examined the allo-responses of peripheral T cells in the lck -/- mice and the following results were thus obtained. (1) After an intravenous injection of fully allogeneic [allo-major histocompatability complex (MHC)] spleen cells, an increase of interleukin (IL)-2R alpha+ cells was observed in both the CD4+ or CD8+ peripheral T cells of the lck -/- mice and the increase was similar to those in the lck +/+ littermate, with only a somewhat delayed and prolonged time kinetics observed in the CD4+ T cells of the lck -/- mice. (2) the lck -/- mice rejected the fully allogeneic trunk skin grafts several days later than the lck +/+ mice, but did not reject the minor allogeneic grafts. (3) The peripheral T cells of the graft-rejected lck -/- mice exhibited a weaker but significantly proliferative response, while the cytotoxic T lymphocyte (CTL) activities to allo-MHC antigens in vitro were comparable to those in lck +/+ mice. While the response to the minor allo-antigens was shown by the peripheral T cells in the lck +/+ mice with minor allogeneic skin grafts but not by those in the lck -/- mice with the grafts. These results thus suggest that p56lck is not essential for peripheral T cells to both respond and exhibit effector functions to allo-MHC antigens.