When thoracic duct lymphocytes (TDL) or mesenteric lymph node (MLN) cells from mice primed 1 day before with either sheep erythrocytes (SRC) or horse erythrocytes (HRC) were transferred together with both SRC and HRC to irradiated mice, antibody responses measured 7 days later could not be detected to the priming antigen but were high to the other antigen. Furthermore, this unresponsiveness of TDL and MLN to the priming antigen could not be abrogated by delaying antigen challenge of the transferred cells for 1-2 wk. Previous work had shown that short-term priming with antigen also induced specific unresponsiveness in spleen cells on adoptive transfer. Unresponsiveness in these cells, however, was only of temporary duration, full recovery in the reactivity of the cells being observed when challenge with the priming antigen on transfer was delayed for 5 or more days. Since the present work showed that such recovery from initial unresponsiveness on transfer was unique to spleen cells and did not apply to TDL or MLN, it appeared that different mechanisms were responsible for the unresponsiveness in the three populations. It is proposed that the unresponsiveness detected in TDL and MLN cells in the present study resulted from a deficiency of antigen-reactive cells, these cells having been recruited to the spleen, i.e., a region of antigen concentration. This concept of antigen-induced selective recruitment of circulating lymphocytes was supported by evidence that (51)Cr-labeled heterologous erythrocytes indeed localized largely in the spleen after intravenous injection but not in MLN.