The alymphoplasia (aly) mutation of mice causes the systemic absence of lymph nodes, Peyer's patches and well-defined lymphoid follicles in the spleen. We found that antibody responses are elicited, albeit weakly, to either T cell-dependent or T cell-independent antigen by aly/aly mutants. However, isotype switching was defective. The T cell-dependent immune response was not elicited in splenectomized aly/aly mice. Neither hypermutation nor germinal center formation was observed in aly/aly mice. These results suggest that T-B collaboration requires either lymph nodes or spleen, and that hypermutation and affinity maturation depend on germinal center formation.