BACKGROUND The treatment of Hodgkin's disease (HD) involves irradiation and chemotherapy. Both modalities may cause heart and lung injury. We aimed to assess 1) the occurrence of such injury, 2) the extent to which combined versus single-organ-affection resulted in disability, and 3) whether determinants for cardiopulmonary injury could be identified. METHODS A national cohort (n = 116) of HD patients (mean age 37 +/- 7 (SD) years, 67 males) was examined by interview, echocardiography, bicycle exercise test and lung function tests, 5-13 years after mediastinal irradiation with or without chemotherapy. RESULTS Cardiac, pulmonary or combined sequelae occurred, respectively, in 21%, 15% and 19% of the patients affecting 75% of the females versus 41% of the males (P < 0.001). Of the patients with combined sequelae, 27% were disabled versus 4% of the rest (P < 0.05). Combined sequelae was associated with dyspnoea (P < 0.001) and reduced maximal exercise heart rate (P < 0.05). Compared to males, females had an increased risk of heart valve regurgitation (46% versus 16%, P < 0.001), pericardial thickening (22% versus 10%, P = 0.07) and reduced gas transfer (41% versus 22%, P = 0.03). Female gender was a significant risk factor for cardiac and/or pulmonary sequelae (OR 6.1, 95% CI 2.4-15.7), whereas age, follow-up period, smoking habits, histology, bulky mediastinal disease, radiation dose and chemotherapy were not. Mean exercise work capacity and O2-saturation were within normal limits. CONCLUSIONS Although cardiac and/or pulmonary sequelae were detected in more than half of the patients, only combined injury was associated with disability, dyspnoea and reduced performance. Females had an increased risk of cardiopulmonary sequelae, which could not be explained by treatment-related differences between the genders.