Spleen cells from CBA/N mice with an X-linked B cell defect were examined for their ability to form antibody in vitro after stimulation with the T-independent antigen TNP-LPS. In contradistinction to their failure to respond to some conventional T-independent antigens such as type III pneumococcal polysaccharide or DNP-AECM-Ficoll, spleen cells from (CBA/N X DBA/2)F1 male mice were able to make a specific anti-TNP PFC response after culture with TNP-LPS. Their response differed from that of phenotypically normal (CBA/N X DBA/2)F1 female littermate spleen cells in that more TNP-LPS was required to elicit the peak anti-TNP response and the anti-TNP antibody secreted by F1 male cells was of lower avidity than that of F1 female cells. The polyclonal antibody response to unsubstituted LPS did not differ substantially between normal and defective B cells. Tnymus-derived cells were not required for the TNP-LPS response by either F1 male or female cells. We conclude that CBA/NB cells can respond to certain T-independent antigens that are able either to induce a very strong activating signal upon ligand-surface receptor interaction and/or to stimulate immature B cells (with a characteristic high surfact immunoglobulin profile) which fail to respond to antigens like DNP-AECM-Ficoll.