An 8-week-old female infant presented with a history of active varicella complicated by Escherichia coli sepsis, oral thrush, hypoalbuminemia, intermittent fevers, diarrhea and feeding intolerance. Rhesus monkey kidney cells inoculated with cerebrospinal fluid revealed reovirus-like particles by electron microscopy. Virus neutralization and RNA-gel electrophoresis studies identified the isolated pathogen as reovirus serotype 2. This report represents one of only a few to isolate reovirus from the central nervous system in humans.