The pharmacokinetics and safety of extended-interval dosing of prophylactic liposomal amphotericin B (L-AMB) in peripheral stem cell transplant recipients were evaluated. The patients received L-AMB daily at 1 mg/kg of body weight or weekly at 7.5 mg/kg or received L-AMB as a single dose (15 mg/kg). The buccal mucosal tissue concentrations of L-AMB were measured. Of the 24 patients enrolled, 5 withdrew after the initial dose due to an infusion-related reaction (n 2) or significant increases in the serum creatinine (Scr) levels (n 3). Weekly L-AMB dosing (7.5 mg/kg) produced mean plasma concentrations of>0.300 g/ml for the first 7 days and>0.220 g/ml for 7 days after the second dose. A single L-AMB dose (15 mg/kg) produced mean plasma concentrations of>0.491 g/ml for at least 7 seven days. These concentrations are within the range of the MICs reported in the literature for susceptible strains of Candida and are at the lower limits of the MICs for Aspergillus spp. Extended-interval dosing produced buccal mucosal tissue concentrations well in excess of the MICs reported in the literature for susceptible strains of Candida and Aspergillus spp. Infusion-related reactions occurred in 24 % of the patients. Baseline and end-of-study Scr, electrolyte (K, Mg2, PO4), and serum transaminase levels were similar across the dosage groups. Five (31%) patients met the nephro-toxicity definition prior to completion of the study. Patients in the weekly or single-dose groups experienced