The rapidly proliferating gastrointestinal mucosa is one of the major limiting tissues in cancer therapy. Because of its short transit time and high sensitivity to radiation and chemotherapeutic drugs, damage is rapidly manifested. Protection of the important stem cells in the tissue could be achieved, in principle, by appropriate prior manipulation with cytokines or growth factors which might make them more resistant to the cytotoxic treatment, for example, by putting them out of cycle. Such strategies might reduce some of the adverse side-effects of cancer treatment and improve the quality of life of patients, while possibly allowing an escalation of therapeutic dose. The functional capacity of stem cells has been studied for many years using a microcolony assay technique which measures the regenerative capacity of the clonogenic stem cells in crypts. These cells determine the survival of crypts which themselves determine whether or not the mucosal integrity is maintained and ultimately whether the animal or patient survives. Here, we demonstrate that treatment with interleukin-11 for 2 days prior to radiation exposure can significantly increase the number of surviving crypts. Treatment with IL-11 both before (for 2 days) and after irradiation (for 3 days) produces a slightly enhanced protection. Up to about 4 times more crypts survive at the highest radiation dose after either of these treatment schedules. These studies may provide a radiobiological explanation for the increased survival of animals when IL-11 is administered during 5FU and radiation exposures.