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The incidence of human granulocytic ehrlichiosis (HGE) in the upper Midwest is uncertain. Active surveillance for suspected HGE was conducted from 1997 through 1999 in a 13-county region of northwestern Wisconsin. Suspected HGE cases were classified, according to the national case definition, as confirmed, probable, or not HGE. In total, 112 confirmed cases and 30 probable cases of HGE were identified. The median age of the 142 case patients was 56 years, and 92 (65%) were male; 111 (78%) were residents of the surveillance region. The mean annual incidence of confirmed and probable HGE was 9.3 cases per 100,000 residents; there was no increase from 1997 to 1999. The incidence was highest among persons > or =50 years old and residents of Washburn County. The incidence of HGE in this region exceeded prior estimates, but it was lower than the reported incidence in areas of endemicity in Connecticut.