Thymocytes and spleen cells from C57BL/6 mice (H-2b) neonatally tolerized to H-2k alloantigens do not generate an anti-vaccinia response restricted to H-2Kk when adoptively transferred to appropriate irradiated hosts. This is in sharp contrast to the case for negatively selected C57BL/6 spleen cells acutely depleted of alloreactivity. No evidence for suppression was found in cell mixture experiments. We have shown elsewhere that our neonatally tolerized animals have a centrally induced delection-type tolerance in the absence of obvious suppression.2 We now suggest that in the neonatally tolerized mouse, chronic, central delection of anti-H-2k clones during early T cell ontogeny eliminates the major source of cells able to give rise, via somatic mutation and expansion, to anti-H-2Kk + vaccinia specific cytotoxic T lymphocyte precursors (CTL-P) in the adult. A similar mechanism may operate in the (k + b) leads to b chimera; however, the presence of H-2kxb accessory and presenting cells may permit the eventual generation (via cross-stimulation) of an H-2k-restricted vaccinia-specific repertoire. This would account for our observation of such "aberrant recognition" CTL-P emerging in the spleens of older (k x b) leads to b chimeras.