The purpose of this trial was to evaluate the efficacy and the tolerance of high-dose therapy with autologous stem cell transplantation as part of front-line therapy in Hodgkin's disease for patients with both adverse prognostic factors: high tumor burden at presentation and slow response to initial chemotherapy. In a prospective one-center study, 20 consecutive patients with slow response (tumor reduction < 75%) (16 pts) or refractory (4 pts) to 3-4 courses of conventional HD chemotherapy received high-dose therapy followed with autologous bone marrow (14 pts) or peripheral blood stem cell (6 pts) transplantation. They were 13 males, 7 females, median age 26 years (8-45). At the time of initial diagnosis, all but one of the patients had B symptoms, all had high-risk HD defined as Ann Arbor stage IV (7 pts) or large mediastinal involvement (LMI = tumor/thorax > 0.45 at T5-T6) (6 pts) or both stage IV+LMI (7 pts). Median time between diagnosis and autotransplantation was 5 months. Intensive therapy consisted of either CBV (cyclophosphamide 1.5 g/m2 x 4, BCNU 300 mg/m2, etoposide 200 mg/m2 x 3) (12 pts) or cyclophosphamide 120 mg/kg + 12 Gy total body irradiation for 8 patients with diffuse bone or lung involvement. For pts treated with CBV, 40 Gy involved field radio-therapy was performed after hematological recovery. Median duration of neutropenia was 16 days (9-21). Neither veno-occlusive disease, nor interstitial pneumonitis nor toxic death were observed. Seventeen pts are alive with no progression of the disease (16/16 in partial response after initial chemotherapy, 1/4 with refractory disease).(ABSTRACT TRUNCATED AT 250 WORDS)