Busulfan has been previously only available in an oral formulation due to its poor water solubility. We report the results of a phase I study of multiple escalating doses of intravenous busulfan (Spartaject Busulfan, Orphan Europe, Paris, France) for myeloablation prior to stem cell transplantation (SCT) in 12 patients with chronic myeloid leukemia, acute myeloid leukemia or acute lymphocytic leukemia. One patient received allogeneic SCT; the other 11 patients received autologous SCT. The first six patients received i.v. busulfan diluted in 50 ml of 0.9% normal saline and the last six patients received busulfan in a 500-ml 5% dextrose solution. All patients experienced profound myelosuppression and all but one demonstrated hematopoietic engraftment. Toxicity was mild or moderate and there were no toxic deaths attributable to busulfan. Of note, there were no cases of veno-occlusive disease of the liver. Busulfan plasma concentrations were determined by gas chromatography with electron capture detection and showed little intrapatient variability. In most cases there was no significant difference between the first and last dose PK parameters. These data suggest that dose adjustment based on first dose PK data could allow uniformity of busulfan dosing for patients receiving SCT.