During the 1991-92 influenza season, sustained regional influenza activity began to be reported by state and territorial epidemiologists in the United States in mid-October 1991. Sustained reporting of widespread influenza activity began in early November 1991, 5-10 weeks earlier than in any of the previous nine influenza seasons. Influenza caused substantial morbidity among school-age children and excess mortality among the elderly. Regional outbreaks of influenza ended 2-6 weeks earlier than in the previous nine influenza seasons, based on the last sustained state and territorial epidemiologists' reports. Nationally, > 99% of isolates were influenza A. Influenza A(H3N2) predominated in all regions of the country, but isolation of influenza A(H1N1) increased proportionally as the season progressed. Isolation of influenza B (< 1% of total isolates) clustered after February. The majority of isolates characterized were antigenically similar to components in the 1991-92 influenza vaccine. However, an influenza A(H1N1) strain that had undergone antigenic drift was detected in many regions of the country; this strain will be included in the 1992-93 influenza vaccine.