The combination of mediastinal radiotherapy (RT) and polychemotherapy (CT) regimens can produce late toxic pulmonary and cardiac effects which often remain at the subclinical level. The aim of the present study was to investigate the cardiopulmonary response to exercise in this kind of patient. Therefore, 126 patients suffering from Hodgkin's disease were investigated after a follow-up of at least 5 years from the completion of the combined treatment. Sixty-two patients had been submitted to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)-RT, 40 to ABVD-MOPP (mechloretamine, vincristine, procarbazine, prednisone)-RT and 24 to VEBEP (vincristine, epidoxorubicin, bleomycin, cyclophosphamide, etoposide, prednisone)-RT. The patients were divided into three groups on the basis of respiratory function: group 1 (67 patients), normal spirometry and lung transfer function for carbon monoxide (DLCO); group 2 (52 patients), normal spirometry and DLCO less than 80% of predicted; and group 3 (7 patients), total lung capacity and DLCO less than 80% of predicted. The patients were submitted to respiratory function evaluation and 2D-echocardiography before exercise, and to the determination of cardiac output by the acetylene rebreathing method before and during symptom-limited exercise on a cycloergometer using an incremental protocol. The patients of group 3 and to a lesser extent the patients of group 2 showed, in comparison to patients of group 1, a lower tolerance to exercise, a lower oxygen consumption, a higher respiratory rate, a lower O2 pulse and a lower cardiac output per oxygen uptake. These data indicated an abnormal exercise physiology in the patients with persistent pulmonary impairment, especially when the reduction of DLCO was associated with a decrease of total lung capacity. The lower exercise capacity seems to be due to a combination of decreased cardiac performance and an impairment of gas diffusion capacity.