Corticosteroids cause impaired cell-mediated immunity which may encourage development of gastrointestinal and respiratory infections. In order to better understand the effects of corticosteroids on gastrointestinal immunity, immunological and histological changes in gut-associated lymphoid tissues were examined after intravenous administration of dexamethasone to rabbits. In treated animals, lymphoid domes and follicles were considerably reduced in size, and the dome epithelial layer was markedly depleted of M cells and lymphocytes. There were numerous open lesions at the luminal surface of dome epithelium, consistent with necrosis of M cells, and a striking depletion of follicular B cells in treated animals. These immunologic and histologic effects of corticosteroids could have found profound, deleterious effects on mucosal immune responses and host resistance to microbial infections.