We studied the pharmacokinetics of busulfan (16 mg/kg) in 16 pediatric patients affected by malignant and nonmalignant disorders between 6 months and 19 years of age (mean +/- SD, 5.7 +/- 6.5 years) who were undergoing allogenic (15 patients) and autologous (one patient) bone marrow transplantation. In all children, the conditioning regimen consisted of busulfan given orally at a dose of 1 mg/kg every 6 hours for 16 doses (total dose, 16 mg/kg), associated with other drugs. The pharmacokinetics of busulfan was studied during the 6-hour dosing interval on the third day of therapy by use of a high-performance liquid chromatographic assay. The value for the time to reach maximum concentration, expressed as mean +/- SD, was 1.1 +/- 0.5 hour; maximum concentration was 609.6 +/- 225.3 ng/ml; steady-state concentration was 358.9 +/- 135.5 ng/ml; area under the plasma concentration-time curve was 2153.6 +/- 813.1 ng.hr/ml; oral clearance was 0.535 +/- 0.226 L/hr/kg; and half-life was 2.4 +/- 0.8 hours. Age-related differences in busulfan disposition were observed. The mean busulfan oral clearance in a group of 10 patients with an age range from 6 months to 3 years was 0.619 L/hr/kg, whereas six patients whose ages ranged from 7 to 19 years had a oral clearance of 0.396 L/hr/kg. The half-lives for busulfan during infancy decrease continuously until early childhood but were prolonged in older children. No significant relationship between systemic exposure to busulfan and drug effect was observed.