To determine the prevalence, severity, and correlates of fatigue among patients with cancers of the prostate or breast receiving high dose radiotherapy with curative intent, a prospective, questionnaire-based study evaluated a convenience sample of 62 patients who were about to start a course of radiotherapy. Patients were assessed immediately prior to treatment, and again within a week of finishing. Fatigue was assessed using the Fatigue Severity Scale (FSS) and the Bidimensional Fatigue Scale (BFS). Quality of life was assessed using the European Organisation for Research and Treatment of Cancer 30-item Quality of Life Questionnaire (EORTC QLQc30). Psychological distress was assessed using the Hospital Anxiety and Depression Scale (HADS). Personality Traits were assessed using the Eysenck Personality Inventory (EPI). Fatigue severity increased significantly on 3 out of the 5 assessment instruments used. Radiotherapy was associated with a decline in global quality of life, role, cognitive and social functioning, and an increase in nausea/vomiting, pain, insomnia, diarrhea, and financial difficulty. At baseline, 39% of the variation in fatigue scores among the patients could be explained by a combination of measures of their global quality of life and physical functioning. A combination of fatigue and anxiety scores at baseline was able to predict 54% of the variation in fatigue scores at the completion of radiotherapy. These data indicate that fatigue is a significant problem for patients receiving radical radiotherapy, although its severity is relatively modest.