Background: When oseltamivir is administered in extremely high doses (500-1000 mg/kg) to young juvenile rats, central nervous system toxicity and death occurred in some animals. Mortality was not observed in older juvenile rats, suggesting a possible relationship between neurotoxicity and an immature blood-brain barrier. To assess potential neurologic adverse effects of oseltamivir use in infants, a retrospective chart review was performed in infants less than 12 months of age who received oseltamivir, amantadine, or rimantadine. Methods: The primary objective was to describe the frequency of neurologic adverse events among children less than 12 months of age who received oseltamivir compared with those receiving adamantanes. Medical record databases, emergency department databases, and/or pharmacy records at 15 medical centers were searched to identify patients. Results: Of the 180 infants identified as having received antiviral therapy, 115 (64%) received oseltamivir, 37 (20%) received amantadine, and 28 (16%) received rimantadine. The median dose of oseltamivir was 2.0 mg/kg/dose in 3-to 5-month-old and 2.2 mg/kg/dose in 9-to 12-month-old infants. The maximum dose administered was 7.0 mg/kg/dose. There were no statistically significant differences in the occurrence of adverse neurologic events during therapy among subjects treated with oseltamivir versus those treated with the adamantanes (P = 0.13). Conclusions: This is the largest report to date of oseltamivir use in children less than 12 months of age. Neurologic events were not more common with use of oseltamivir compared with that of the adamantanes. Dosing of oseltamivir was variable, illustrating the need for pharmacokinetic data in this younger population. © 2010 Lippincott Williams & Wilkins.