From November 1, 1981, through April 30, 1982, we performed a case-control study of primary invasive Haemophilus influenzae infections in children in Colorado. Information was collected for 121 (83%) of 146 children with positive cultures and for 196 (67%) of 292 age-matched controls selected at random from birth certificates. Infected children were more likely to have attended a day care center or nursery (DCC/N) and to have an elementary school-aged household member. For attendance at DCC/N, the relative risk was significantly increased only for children 12 months of age or older, and increased with the size of the DCC/N. After controlling for DCC/N attendance and school-aged siblings, children younger than 6 months of age with infection were significantly less likely to have been breast-fed, suggesting a protective effect of breast-feeding. We identified DCC/N attendees, especially those older than 1 year of age, to be at increased risk of primary H. influenzae disease. They could benefit from immunization.