Thoracic irradiation induced duodenal lesions in mice as an indirect effect. We studied the influence of partial thoracic irradiation on endogenous histamine stores in the alimentary canal. Mice subjected to lower mediastinal irradiation had significantly higher (+19%) median gastric histamine, but lower (-44%) distal duodenal histamine than controls. They also had significantly lower proximal (-39%) and distal (-44%) duodenal histamine than mice who received upper mediastinal irradiation. Twenty-three percent of mice after lower mediastinal irradiation had duodenal lesions; these had significantly lower proximal (-30%) and distal (-44%) duodenal histamine than controls. Thus, irradiation to the lower mediastinum induced both duodenal lesions and significant changes in gastric and duodenal histamine stores. Histamine may be involved in the pathogenesis of these lesions.