Fifty-one consecutive patients with Hodgkin's disease (HD) have been treated with high-dose chemotherapy (HDT) and transplantation of autologous bone marrow (BM) (n = 44), autologous BM plus peripheral blood stem cells (PBSC) (n = 2), PBSC (n = 1), syngeneic (n = 1), or allogeneic BM (n = 3). All patients had received standard salvage chemotherapy prior to HDT and were classified as sensitive (n = 33) or resistant (n = 17) to this treatment; one patient was in untreated relapse prior to BMT. The preparative regimens for patients receiving autologous BM and/or PBSC consisted of cyclophosphamide, VP 16, and BCNU (CVB) (n = 44) or BCNU, etoposide, ara-C, and melphalan (BEAM) (n = 3). The patients receiving allogeneic transplants were treated with the CVB regimen (n = 2) or busulfan (16 mg/kg body wt.) and cyclophosphamide (200 mg/kg body wt.). With a median follow-up of 12 months, overall survival for 44 patients grafted with autologous BM is 61% +/- 9%, progression-free survival for patients with sensitive disease is 44% +/- 11%; no patient with resistant relapse survived beyond 1 year post transplant. Two of three patients grafted with allogeneic BM still survive 15 and 24 months after BMT with Karnofsky performance scores of 70% and 100%, respectively. The main toxicity encountered with the CVB regimen was interstitial pneumonia (IP), seen in four of 15 patients (27%) receiving > or = 600 mg/m2 of BCNU. Three of these patients have died. The results show that HDT followed by hematopoietic stem cell rescue may effectively salvage an important fraction of patients with relapsed HD who respond to standard chemotherapy. The same approach is largely unsuccessful in patients with proven refractoriness to standard chemotherapy. Whether HDT followed by BMT or PBSC support is superior to intensive chemotherapy without stem cell support can be answered only by a prospectively randomized trial.