The primary response of the popliteal node to Salmonella lipopolysaccharide was studied in the sheep. All three classes of immunoglobulin IgG1, igG2, and IgM were produced by both free-floating cells in the lymph and by cells within the pymph node throughout the immune responce which extended over a period of at least 20 days.. Most of the immunoglobulins were found to be nonspecific for the antigen when tested by a binding assay. It was calculated from the binding assay that far more antigen-specific IgG molecules were produced than IgM molecules. The proportion of IgM and IgG1 which showed affinity for Salmonella organisms increased throughout the response. IgG2 had no affinity for the antigen until around 480 h after challenge. When a hemagglutination assay was used to measure antibody production, most of the specific antibody produced during the response was found to be IgM. Blast cells produced most of the immunoglobulin during the first 4 days of the response, and these cells were responsible for almost all of the IgM production. Differences were observed in the relative amounts of IgG and IgM produced by the cells within the node and by free-floating cells in the efferent lymph. The free-floating cells in lymph synthesized and secreted relatively more IgM and relatively less IgG than did cells within the lymph node. Both populations of cells, however, secreted much more IgG than IgM.