CBA/N mice carry an X-linked immune-deficiency gene, leading to a defect in the ability to form antibodies against T-independent type 2 antigens. By using immunohistochemistry, the organization of the spleen of the immune-deficient male (xid) CBA/N F1 and the normal female F1 were compared. Staining with antilymphocyte markers showed that the total number of cells in the various T- and B-cell areas was smaller in the xid mouse, resulting in very small white pulp compartments. Fewer B cells were seen in the marginal zone. When the spleens of the F1 mice were examined for macrophage markers, the rings of marginal-zone macrophages and the ring of marginal metallophilic macrophages were much thinner in the xid mouse. In particular, the marginal-zone macrophages are thought to play a role in the response against thymus-independent type 2 antigens, and their small numbers in the xid mouse are suggestive of a role for the microenvironment in the defects in these mice.