Mice deficient in lymphotoxin-a (LTa"/") have no morphologically detectable lymph nodes or Payer's patches, and they fail to form germinal centers (GC) in the spleen even following repeated immunization with high doses of protein antigens. Absence of GC in the spleen was accompanied by failure to establish the normal marginal zone of metallophilic macrophages (as observed by staining with MOMA-1) and failure to organize clusters of follicular dendritic cells (defined by trapping peroxidase/anti-peroxidase immune complexes and by immunohistochemical staining). These mice afford the opportunity to test whether GC are essential for the normal maturation of antibody responses to T-dependent antigens. When LTa~/~ mice were immunized intraperitoneally with low doses of NP-ovalbumin (NP-OVA), there was dramatically impaired production of high affinity anti-NP IgG; however, following intraperitoneal immunization with high doses ! of NP-OVA, LTa~/~ mice mounted a high affinity NP-specific serum IgG response similar to wildtype mice. These results indicate that the mechanisms responsible for the generation of B cell memory are not absolutely dependent on the presence of GC structures, although GC enhance the orocesses reouired for maturation of the humoral immune response.