Daptomycin is approved for the treatment of complicated skin and skin-structure infections and Staphylococcus aureus bacteremia. We sought to characterize daptomycin single-dose pharmacokinetics and tolerability in young infants. Subjects < 120 days of age with suspected systemic infections were eligible for inclusion. Each subject was given a single 6 mg/kg intravenous dose of daptomycin. An average of 4 postdose concentrations per infant was obtained. Data from 20 infants are presented. Median gestational age at birth and postnatal age were 32 weeks (range: 23, 40) and 3 days (1, 85), respectively. The median area under the concentration curve at 24 hours, volume of distribution, total body clearance and half-life of daptomycin were 262.4 mg×h/L (166.7, 340.2), 0.21 L/kg (0.11, 0.34), 0.021 L/h/kg (0.016, 0.034) and 6.2 hours (3.7, 9.0), respectively. No adverse events related to daptomycin were observed, including changes in creatine phosphokinase concentrations. Daptomycin clearance in young infants was similar to that in children 2-6 years of age and higher than that observed in adolescents and adults.