Outbreaks of hepatitis in day-care centers in Maricopa County, Arizona, were studied over a two-year period to learn which center characteristics affected the spread of hepatitis A. Of the 279 licensed centers, 85 (30%) had outbreaks of hepatitis affecting three or more families. Outbreaks occurred in 63% of centers enrolling infants younger than one year of age, 32% of centers enrolling children one year of age or older, and 2.5% of centers enrolling children two years of age or older (P < 0.0001). Outbreaks were also significantly more frequent in large centers enrolling ≥51 children, centers open >15 hr per day, and centers operated for profit. The introduction of hepatitis into a center was related strongly to the number of hours open and to the size and age enrollment, but the spread of hepatitis was related solely to the presence of children younger than two years of age. These data strongly link the spread of hepatitis A in day-care centers to the presence of very young children and provide a framework for designing disease-control strategies.