(-)-FTC has been shown to have potent antiviral activity against human immunodeficiency virus type 1 and type 2 and hepatitis B virusin vitro . The purpose of this study was to characterize the pharmacokinetics of (-)-FTC in monkeys. Rhesus monkeys were administered 200 μCi of radiolabeled (-)-FTC with 33.3 mg/kg of (-)-FTC intravenously. Concentrations of (-)-FTC and its metabolites in serum, urine, and cerebrospinal fluid were determined by HPLC. Pharmacokinetic parameters were generated by compartmental analysis. Concentrations of (-)-FTC in serum declined in a biexponential manner and were well described by a two compartment model. Total clearance of (-)-FTC averaged 0.67 ± 0.05 L/h/kg (mean ± SD) and steady-state volume of distribution averaged 1.10 ± 0.14 L/kg. The terminal phase half-life of (-)-FTC was 1.6 ± 0.2 h. Renal clearance was the prevalent mode of elimination, with a fraction excreted unchanged in the urine of 63 ± 7%. Two metabolites of (-)-FTC were identified in serum and urine of monkeys: (-)-FTC-glucuronide and 3 -SO-(-)-FTC. Peak metabolite concentrations were observed within 25 min after drug administration. CSF: serum (-)-FTC concentration ratios were time dependent and no metabolites were detected in CSF. (-)-FTC did not appear to undergo significant cleavage to fluorocytosine.