The ventral surface of the tongue of male Fisher 344 rats was used to evaluate the response of oral mucosa to boron neutron capture irradiation. Three hours after i.p. injection of 700 mg/kg of the boron delivery agent p-boronophenylalanine (BPA), the boron concentrations in blood and tongue mucosal epithelium were approximately 21 and 23 microgram (10)B/g, respectively. The doses required to produce a 50% incidence of ulceration with X rays, the Brookhaven Medical Research Reactor thermal neutron beam alone, or the thermal neutron beam in the presence of BPA were 13.4 +/- 0.2, 4. 2 +/- 0.1, and 3.0 +/- 0.1 Gy, respectively. Ulceration of the tongue was evident by 6 to 7 days after irradiation, irrespective of the irradiation modality; healing was related to dose and was relatively rapid (</=19 days). Compared to 100 kVp X rays, the relative biological effectiveness factors were 3.2 for the thermal neutron beam and 4.9 for the products of the boron neutron capture reaction, (10)B(n,alpha)(7)Li. Oral mucosa is highly sensitive to BPA-mediated BNC irradiation and could be a dose-limiting normal tissue in BNCT of brain tumors, or if BPA-based BNCT is applied to the treatment of head and neck tumors.