Vasoactive intestinal peptide (VIP) is known to modulate inflammatory reactions, to have trophic effects, and to contribute to diarrhea and has been implicated as an important factor in several inflammatory conditions in the human gut. The aim of the present study was to investigate the effects of irradiation on the expression of VIP in the colon of patients operated on for adenocarcinoma. Some of the patients had received preoperative irradiation (25 Gy) within one week before the operation. Specimens of sigmoideum, 10 cm cranial to the margin of the cancer, were examined, by using antiserum against VIP and immunohistochemistry. There were numerous nerve fibers showing VIP-like immunoreactivity in the damaged mucosa, including the regions showing ulcerations. There was a higher degree of expression of VIP in the ganglion cells in the submucous plexuses in irradiated than nonirradiated patients. The study shows that there is a marked immunohistochemical expression of VIP concomitant with the occurrence of inflammatory and repair processes in the irradiation-damaged human colonic mucosa.