The intestine, being highly sensitive to radiation injury, is the limiting factor in the delivery of abdominal and pelvic radiation. Attempts at intestinal radioprotection have generally involved systemic administration of agents that are moderately toxic and that may protect the target malignancy. The lumenal route for intestinal radioprotection provides a high concentration at the mucosa without significant systemic effects. This paper reviews studies of intestinal radiation radioprotection by intralumenal agents. Our model involved irradiation of exteriorized rat small bowel containing drugs in isolated segments. Surviving crypts were quantitated as a measure of injury 5 days later and the individual segments were compared. Modest protection was found with lumenal alkalinization and with neutralization of bile salts or pancreatic enzymes. Similar protection was identified with some nonsteroidal anti-inflammatory agents, methylprednisolone, and selected antioxidants. Marked protection was observed with lumenal Lazaroid.