Neuropeptidergic synthesis occurs in enteric nerves and immune cells of the gut-associated lymphoid tissue. Lymphocytes, macrophages, mast cells, and intestinal epithelial cells are capable of responding to these neuropeptides. Neuropeptides generate proliferative or antiproliferative responses of mucosal lymphocytes and intestinal epithelial cells, affect cytokine production and immunoglobulin synthesis by immune cells, and control secretion of water and electrolytes. Some neuropeptides, particularly cholecystokinin, gastrin-releasing peptide, and neurotensin, appear promising to maintain mucosal immunity in patients who cannot receive enteral feeding during critical illness or after GI tract loss. Exogenous administration of neuropeptides to preserve normal immune defenses represents a potential new field of pharmacotherapeutics against bacterial invasion.