At Indiana University, we began clinical trials with ifosfamide in 1981. Although our initial efforts were in a variety of tumor types, including pancreatic cancer, we have most recently focused our attention on two tumors that have historically exhibited a higher degree of chemosensitivity--testicular cancer and small cell lung cancer (SCLC). In phase II trials, ifosfamide has proven to have single-agent activity in both diseases. Coupling this data with preclinical observations of synergy with cisplatin and etoposide, we began trials of ifosfamide plus cisplatin with either vinblastine (VeIP) or etoposide (VIP) in patients with recurrent germ cell tumors; we also investigated the use of VIP in SCLC. In third-line or greater therapy for recurrent germ cell tumors, a 36% disease-free status was attained, with 16% of patients continuously free of disease for 5 or more years. Currently, ifosfamide is being evaluated as part of initial therapy in patients with advanced disease. In SCLC, VIP has also been investigated as part of initial therapy in patients with extensive disease. The complete response rate of 38% achieved in 37 evaluable patients has spurred the Hoosier Oncology Group to compare the VIP regimen to cisplatin/etoposide in patients with extensive-disease SCLC. Ifosfamide has the broad range of clinical activity, but its ultimate role as part of initial therapy remains to be discerned.