MEDI-493, a humanized monoclonal antibody to the F-protein of RSV, is highly active against RSV. The objective of this study was to describe the safety, tolerance, immunogenicity, pharmacokinetics and clinical outcome of a single intravenous (IV) dose of MEDI-493 administered at 5 or 15 mg/kg in children hospitalized with acute RSV infection. Sixty previously healthy children ≤24 months of age were enrolled at 10 centers. The first 16 children were randomized to receive 5 mg/kg MEDI-493 or placebo while the next 44 were randomized to either 15 mg/kg MEDI-493 or placebo. Adverse events(AEs) MEDI-493 concentrations (CONC), and anti-MEDI-493 binding were monitored. Fifty-nine children received study drug as follows: placebo (n=29), 5 mg/kg MEDI-493 (n=8), or 15 mg/kg MEDI-493 (n=22). AEs were balanced between groups at each dose level and were generally those expected in children hospitalized with RSV infection. One child in the placebo group died from progressive RSV infection. Mean serum CONC in the 15 mg/kg group were 303μg/mL 60 minutes, 144 μg/mL 2 days, and 38 μg/mL 30 days. Non-specific, transient, low-level anti-MEDI-493 binding was observed in ten patients (5 each in the placebo group and MEDI-493 groups). There was no evidence of enhancement of RSV illness. Compared to the placebo group, the 15 mg/kg MEDI-493 group had fewer hospital days per 100 children (276 vs. 466), admissions to ICU (4.5% vs. 19.0%), days of ICU per 100 children (18 vs. 113), days of mechanical ventilation per 100 children (13 vs. 43), days of supplemental oxygen per 100 children (218 vs. 348), and days in hospital with lower respiratory illness (LRI) score ≥3 per 100 children (91 vs. 162), but the differences were not statistically significant. MEDI-493 appeared to be safe and well tolerated when given IV to children hospitalized with acute RSV disease. Serum MEDI-493 CONC well above those which result in greater than a 2-log reduction of pulmonary RSV in cotton rats were achieved with a 15 mg/kg dose and were maintained for 30 days in most children. CONC and AE profiles were similar to those previously reported in children without RSV infection. Trends toward shorter duration of hospital stay and lesser severity of illness were seen in children receiving 15 mg/kg MEDI-493.