Background: Treosulfan (Ovastat®), a bifunctional alkylating cytostatic, indicated for the treatment of advanced ovarian carcinoma, was recently found to be active in human lung and breast carcinoma xenografts. Moreover, toxicological evaluation as well as clinical experience revealed the lack of significant nonhematological toxicity which makes treosulfan a promising candidate for high-dose chemotherapy combined with autol-ogous blood stem-cell reinfusion. As a prerequisite for clinical high-dose studies, a formal phase I dose escalation without stem-cell reinfusion was conducted to reassess the maximum tolerated dose and dose-limiting toxicity of treosulfan after intravenous short-term infusion. Patients: A total of 12 patients with chemotherapy-refractory advanced cancer were entered at 3 dose levels (8 g; 10 and 12.5 g/m2 treosulfan i.v). Most patients suffered from advanced small-cell lung cancer (5 patients) or ovarian carcinoma (3 patients). Results: The maximum tolerated dose of treosulfan in this group of heavily pretreated patients was 10 g/m2. The dose-limiting toxicity was reversible thrombocytopenia. There were no nonhematological side effects exceeding WHO grade 2. Conclusions: This phase I dose escalation trial confirmed the lack of significant nonhematologic side effects of treosulfan although a dose of 12.5 g/m2 was infused. A subsequent phase I study of high-dose treosulfan followed by peripheral blood progenitor cells has therefore been initiated