Mice injected from day of birth onwards with rabbit anti-mouse IgM (antim-mu) antibodies were found to be B cell-deficient and defective for the induction of antigen-reactive proliferating T cells (TPRLF). This defective induction was not due to the absence of circulating antigen-specific antibodies since the daily injections of such antibodies during exposure to antigen did not restore the ability of anti-IgM treated animals to generate TPRLF. Analyzing the cellular events implicated in the induction of virgin antigen-reactive T cells, anti-mu-treated mice manifested impairment of the three interacting cell types involved in the induction of TPRLF. Thus, peritoneal and splenic antigen-presenting cells from such animals were impaired in their capacity to signal a primary antigen-specific T cell reaction. Their splenic lymphocytes could not function as initiator cells in transferring immunogenic signals to recruit TPRLF in normal recipients. Potent antigen-specific splenic initiator cells failed to induce the recruitment of specific TPRLF in anti-mu-treated mice. The defective induction of TPRLF in anti-mu-treated mice may be due to a functional impairment of cells expressing membrane-bound IgM molecules which seemingly play a central role in the transfer of immunogenic signals for the recruitment of antigen-specific circulating T cells. We suggest that splenic B cells function as initiators in the transfer of antigen-induced signals from peritoneal antigen-presenting cells to T cells. These seems to be the primary targets of anti-mu treatment.