The safety, tolerance, and pharmacokinetics of amphotericin B lipid complex (ABLC) were studied in a cohort of pediatric cancer patients. Six children with hepatosplenic candidiasis (HSC) received 2.5 mg of ABLC/kg of body weight/day for 6 weeks for a total dosage of 105 mg/kg. Mean serum creatinine (0.85 +/- 0.12 mg/dl at baseline) was stable at the end of therapy at 0.85 +/- 0.18 mg/dl and at 1-month follow-up at 0.72 +/- 0.12 mg/dl. There was no increase in hepatic transaminases. Mean plasma concentrations over the dosing interval (C(ave)) and area under the curve from 0 to 24 h (AUC(0-24h)) increased between the first and seventh doses but were similar between doses 7 and 42, suggesting that steady state was achieved by day 7 of therapy. Following the final (42nd) dose of ABLC, mean AUC(0-24h) was 11.9 +/- 2.6 microg h/ml, C(ave) was 0.50 +/- 0.11 microg/ml, maximum concentration of the drug in whole blood was 1.69 +/- 0.75 microg/ml, and clearance was 3.64 +/- 0.78 ml/min/kg. Response of hepatic and splenic lesions was monitored by serial computerized tomographic and magnetic resonance imaging scans. The five evaluable patients responded to ABLC with complete or partial resolution of physical findings and of lesions of HSC. During the course of ABLC infusions and follow-up, there was no progression of HSC, breakthrough fungemia, or posttherapy recurrence. Hepatic lesions continued to resolve after the completion of administration of ABLC. Thus, ABLC administered in multiple doses to children was safe, was characterized by a steady state attainable within 1 week of therapy, and was effective in treatment of HSC.