Antigenic competition between sheep red blood cells (SRBC) and horse red blood cells (HRBC) was shown to be thymus-dependent. Mice deprived of thymus-derived lymphocytes (T cells) were not affected in their response to HRBC by a prior injection of SRBC, even after adjuvant treatment. Mice reconstituted with 6 × 107 thymocytes and inoculated only with HRBC made more anti-HRBC antibody than did mice reconstituted with 1.5 × 107 thymocytes. However, after a prior injection of SRBC the situation was reversed: mice with more T cells now made less anti-HRBC antibody than did mice with fewer of these cells. The addition of various lymphoid cells to mice undergoing antigenic competition could not overcome it; indeed, the addition of thymocytes magnified it. Normal spleen cells given to mice lethally irradiated 2 days (but not 6 days or 1 hr) after the inception of an anti-SRBC response were impaired in their ability to respond to HRBC. The amount of interference produced by SRBC on the subsequent response to HRBC did not correlate with the amount of anti-SRBC antibody made. We suggest that the most likely interpretation of these data is that T cells make, in response to antigenic stimulation, a factor which temporarily inactivates other immunocompetent cells.