Short-term preoperative radiotherapy in combination with surgery has been shown to decrease the rate of local recurrence in rectal cancer patients. The effects of this type of radiotherapy on the histopathology of rectal carcinoma has been hitherto unknown. Since various histopathological factors are associated with prognosis, the study of alterations induced by irradiation is an important issue. This paper examines the histopathology of resection specimens from 1306 patients who were treated in a randomized trial that evaluated the benefits of preoperative radiotherapy. In this trial, patients were treated with short-term radiotherapy (5 x 5 Gy) and operated on within 5 days after radiation. Histopathological parameters were determined by the Pathology Review Committee of the trial and we compared tumours of patients with and without preoperative radiotherapy. Tumours of patients who were treated with preoperative radiotherapy were smaller, more often mucinous carcinomas (13% versus 7%, p < 0.001) and more often poorly differentiated (35% versus 24%, p<0.001). After radiotherapy, there was less inflammatory reaction around the tumour (extensive in 7% versus 18%, p<0.001), which was mainly caused by a decrease in T lymphocytes and neutrophil granulocytes. The fibroblastic reaction was more pronounced in the radiotherapy group (extensive in 22% versus 10%, p <0.001). Remarkable histological alterations occurred within a week after 5 days of irradiation of rectal carcinomas. The prognostic value of these factors therefore needs to be re-evaluated for irradiated patients.