The effect of the neuropeptides bombesin and vasoactive intestinal peptide, as well as neurotensin, on natural killer activity by lamina propria mononuclear cells isolated from histologically normal mucosa was assessed. Bombesin and vasoactive intestinal peptide were found to dose-dependently stimulate natural killer activity against Caco-2 colon carcinoma target cells, especially in a short incubation assay, whereas no alterations of cytotoxicity were found against K-562 target cells. Neurotensin, on the contrary, was not found to affect this type of cellular cytotoxicity. Differences in the modulatory effects of these gastrointestinal peptides on natural killer activity by lamina propria mononuclear cells may be related to the distinct localization differences of these peptides within the bowel. The present findings illustrate the existence of neuro-immune interactions at the intestinal mucosa level.