The intestine, being highly sensitive to radiation injury, is the limi
ting factor in the delivery of abdominal and pelvic radiation. Attempt
s at intestinal radioprotection have generally involved systemic admin
istration of agents that are moderately toxic and that may protect the
target malignancy. The lumenal route for intestinal radioprotection p
rovides a high concentration at the mucosa without significant systemi
c effects. This paper reviews studies of intestinal radiation radiopro
tection by intralumenal agents. Our model involved irradiation of exte
riorized rat small bowel containing drugs in isolated segments. Surviv
ing crypts were quantitated as a measure of injury 5 days later, and t
he individual segments were compared. Modest protection was found with
lumenal alkalinization and with neutralization of bile salts or pancr
eatic enzymes. Similar protection was identified with some nonsteroida
l anti-inflammatory agents, methylprednisolone, and selected antioxida
nts. Marked protection was observed with lumenal Lazaroid.