Jejunal response in adult BALB/c mice was studied after acute (15.0 Gy) and fractionated irradiation (2.5 Gy x 6, 5.0 Gy x 3 or 7.5 Gy x 2) with or without 30 min prior injection of fractionated doses of misonidazole (MISO) or bleomycin (BLM). The crypt survival, crypt and villous cellularity, mitotic index and cell death in the jejunal cross section on day 3 post treatment was evaluated. Acute irradiation produced extensive damage to the jejunal mucosa with almost complete loss of crypts and collapse of villi. Dose fractionation resulted in significant tissue sparing with restoration of near normal histology. MISO administered prior to irradiation significantly reduced the crypt survival and increased the mitotic activity and abnormal divisions. But the crypt and villous cellularity remained within the irradiated control range. BLM produced a higher enhancement of the radiation damage, significantly reducing both crypt survival and crypt and villous cell populations. The protective effect of radiation dose fractionation was counteracted by the drug pretreatment. The results warrant caution in the use of these drugs with radiation in the treatment of abdominal malignancies.