We describe two patients with invasive thymomas who responded to high-dose chemotherapy followed by peripheral blood stem cell transplantation (PBSCT) combined with surgery and radiotherapy. The first patient was a 42-year-old man admitted to the hospital with chest pain, and the second patient was a 45-year-old man admitted with myasthenia gravis. Both patients had nonresectable thymomas (stage IVa) because of invasion of the aorta, pulmonary artery, or both, and dissemination to the pericardium. They initially received two cycles of chemotherapy consisting of adriamycin (40 mg/m(2), day 1), cisplatin (50 mg/m(2), day 1), vincristine (0.6 mg/m(2), day 3), and cyclophosphamide (700 mg/m(2), day 4) at 3-week intervals. Four weeks later, they were administered high-dose etoposide (300 mg/m(2), days 1 to 5) followed by granulocyte colony-stimulating factor (G-CSF) [50 micro g/m(2)/d] subcutaneously to mobilize stem cells into the blood. After two additional cycles of adriamycin, cisplatin, vincristine, and cyclophosphamide (ADOC), the patients received high-dose ifosfamide (1.5 g/m(2), days 1 to 4), carboplatin (400 mg/m(2), days 3 to 5), and etoposide (200 mg/m(2), days 1 to 5) followed by PBSCT. They were administered G-CSF (50 micro g/m(2)/d) after PBSCT, with subsequent rapid recovery of neutrophil and platelet level. The tumors shrank remarkably, and could be excised completely in both patients. Postoperatively, 50 Gy of irradiation was administered. Disease-free status has been maintained for 5 years in the first patient and 2 years in the second patient. Our findings suggest that high-dose ifosfamide, carboplatin, and etoposide followed by PBSCT in combination with an ADOC regimen, surgery, and radiotherapy is very effective and well tolerated in patients with advanced nonresectable thymoma.