Late radiation enteropathy (LRE) is a serious disorder, and therapeutic progress has thus far been hampered by insufficient understanding of the pathogenesis. This prospective study addresses whether alterations in proximal intestinal motility can predict the clinical severity of this disorder. Forty-one consecutive patients with chronic abdominal complaints after radiotherapy for gynecological cancer were examined by prolonged ambulatory manometry. Twenty-seven healthy adults served as controls. Impaired fasting motility was found in 12 of 41 patients (29%), and attenuated postprandial motor response after a liquid-solid meal was seen in 10 of 41 patients (24%). Postprandial delay of the migrating motor complex (MMC) was a good predictor of the degree of malnutrition (Cox regression,P<0.01), and intensity of the MMC and postprandial motility index explained 69% (P<0.001, multiple regression) of the variability in degree of malnutrition, assessed by weight loss and serum albumin level. The typical presentation of severe LRE was clinical symptoms suggesting intestinal pseudoobstruction, malnutrition, failure of a liquid-solid meal to induce postprandial motility, and delayed initiation and reduced intensity of MMC during nocturnal fasting. Prolonged ambulatory manometry was useful for detection of dysmotility in patients with symptoms of LRE and impaired motility of proximal small intestine seems to be a key factor in the pathogenesis of severe LRE.