Children with metastatic retinoblastoma are considered to have a poor prognosis after conventional chemotherapy. We used high-dose chemotherapy (HDC) with peripheral hematopoietic stem cell transplantation in such patients in an attempt to improve their survival. Four patients with bone marrow metastases and one child with extraorbital disease were treated with HDC after achieving complete remission by enucleation and conventional chemotherapy. The child with extraorbital tumor was the only one to receive local irradiation. The conditioning regimen included thiotepa (900 mg/m(2)), etoposide (40 mg/kg) and carboplatin (1.5 g/m(2)) in four patients, and BCNU (300 mg/m(2)), cyclophosphamide (6.8 g/m(2)) and etoposide (1.6 g/m(2)) in one child. Hematologic recovery occurred without delay in all patients. The main toxicities were diarrhea, mucositis and infectious complications. No toxic deaths or any major late toxicities were observed. The child treated with the BCNU regimen developed a meningeal relapse 10 months after HDC, which was partially resected and treated with conventional chemotherapy, but not with radiotherapy. He is in complete remission (CR) 105 months off treatment. The other patients are in CCR for 107, 57, 9 and 8 months after HDC. HDC with thiotepa, etoposide and carboplatin may represent a curative option for children with extrabulbar or disseminated retinoblastoma responsive to chemotherapy. It may control occult CNS disease. The necessity to irradiate these children and the curative potential of this strategy for patients with bulky CNS disease remain to be determined.