Immunologic changes may play a role in the pathogenesis of Crohn's disease. Whether these changes are the primary cause of the disease or secondary to the inflammatory response remains unknown. Activated T helper cells probably play a pivotal role in Crohn's disease, although no causative antigen has been identified. Possible targets for immunomodulating therapy should include neutralization of the antigens, deletion of reactive activated T cells or, less specifically, interference with the antigen-presenting process. New, humanized, monoclonal antibodies that interfere with the antigen-presenting process are now available for clinical investigation. In particular, CD4 antibody treatment seems of interest, in view of the predominant role of T cells in Crohn's disease. Finally, because tumor necrosis factor is necessary for granuloma formation, inhibition of this factor may be expected to improve disease activity in Crohn's disease.