Mice injected at birth with the thymus-independent type 2 antigen TNP-AECM-Ficoll have augmented anti-TNP antibody responses when their spleen cells subsequently are challenged in vitro with TNP-coupled thymic independent or thymic dependent antigens. This neonatal priming effect was shown to occur in neonatal nu/nu mice and thus does not appear to require T lymphocytes. The primary explanation for the priming effect seems to be an increase of approximately 10-fold in the numbers of TNP-specific precursors of antibody-forming cells. The neonatal injection of TNP-AECM-Ficoll induces little or no antibody formation directly. It appears, therefore, that some thymic independent antigens can deliver a signal to immature B cells, which causes clonal expansion, but is unable to induce differentiation into antibody-forming cells.