To assess the prognostic significance of mediastinal involvement of Hodgkin's disease, 91 patients with stage I to III disease treated at our Institute were reclassified according to size of mediastinal disease and other clinical and therapeutic characteristics. Complete remission (CR) was achieved in 46 of 67 (81%) patients without mediastinal involvement, and in 16 of 17 (94%) patients with small mediastinal masses, but only in 10 of 17 (59%) patients with large masses (P less than 0.05). Twenty-seven of 32 (84%) patients treated with irradiation alone and 26 of 28 (93%) patients treated with combined modality therapy reached a CR, whereas such a result was obtained only in 19 of 31 (61%) patients who received MOPP chemotherapy alone (P less than 0.01). In particular, none of the patients with large masses had a CR when treated with chemotherapy alone, whereas no differences in response to therapy were found between patients with large vs. small or no masses when irradiation or combined treatments were utilized. Since combined treatment seems to reach a high proportion of CR and to prevent extranodal relapse, further randomized clinical trials are needed to decide its routine utilization in patients with poor prognostic factors such as large mediastinal adenopathies.