A recent clinical protocol combining retinoic acid, interferon, and radiotherapy for advanced cervical cancer produced proctitis severe enough to necessitate dose reductions. In an attempt to model this biological response to multimodality therapy, we used a murine model to study the response of the colonic epithelium. Mice were treated with retinoic acid (100 micrograms/day) and interferon (3 x 10(4) units/day) for 5 days before undergoing whole-body irradiation. The functional response of the bowel was assessed by the ability to maintain body weight, and reproductive cell survival was quantified by the colon crypt assay. Both assays indicated a moderate protective effect of treatment with retinoic acid and interferon prior to irradiation. Protection factors in the range of 1.1-1.4 were observed.