alpha-Interferon (IFN) blood levels were studied in 38 children hospitalized for rotavirus gastroenteritis. During rotavirus infection, a peak of systemic alpha-IFN was observed within 2 days of onset of symptoms. There was a significant positive correlation between alpha-IFN levels and the number of vomiting episodes (p = 0.0003) but not with duration of vomiting, maximal temperature, and duration of fever. alpha-IFN levels were higher in children with peripheral cyanosis compared with children without peripheral cyanosis (p = 0.005) and tended to be higher in children with diarrhea of < 3 days' duration compared with those with diarrhea lasting > 4 days (p = 0.06). alpha-IFN could be partly responsible for the severity of such initial symptoms as vomiting and peripheral cyanosis in rotavirus gastroenteritis and could play a role in recovery from diarrhea.