Experiments were performed to test the hypothesis that Ly-1 B cells respond to antigenic challenge with LPS from gram-negative bacteria. To perform these experiments, the splenic fragment culture system for the study of B cell precursors was used. We found that a significant number of anti-O/core, but not anti-lipid A, precursors expressed the lambda L chain. A restriction of the anti-LPS response to Ly-1 B cells was tested using a Ly-1 depletion protocol. We found that the anti-O/core antibody response was restricted to the Ly-1 B cell lineage. In contrast, conventional B cells, not Ly-1 B cells, respond to an antigenic challenge with lipid A. Our results further support the idea that the Ly-1 B cell lineage serves a direct role in protecting against certain bacterial infections.