Summary: The kinetics of induction of immunologic unresponsiveness to human γ-globulin (HGG) were studied in the adult C57BL/6 mouse using a cell transfer system. Either 0.5 or 5.0 mg soluble HGG was injected into mice and spleen cells transferred to lethally irradiated, isologous recipients which were then challenged with HGG in adjuvant. When the cells of the donor had been in contact with soluble HGG for 5 or more days, they did not respond to challenge after transfer. Cells transferred before 5 days were able to make an antibody response indicating that there is an induction period of at least 4 days in the establishment of immunologic unresponsiveness. Cells transferred before 5 days, but not challenged in the recipient until well after the induction period, i.e., 8 days, were still able to respond, indicating that extracellular antigen is needed throughout the induction period. The induction period is not observed when soluble form of HGG is followed by HGG in adjuvant in the same animal. This is probably due to a competition between soluble and adjuvant forms of the antigen.