A day care center for the short term care of mildly ill children opened in Minneapolis in October, 1985. We conducted a prospective study to evaluate the risk for study participants of acquiring subsequent infections as a result of possible exposure to other infectious agents while at the center. Between June, 1986, and August, 1987, we determined the rates of subsequent infections for 118 children attending the day care center (center-based children) and compared them with rates of subsequent infections for children participating in a home-based sick child care program (home-based children). Of 105 center-based children potentially exposed to respiratory illness while at the center, 24 (23%) developed subsequent respiratory illness compared with 17 (16%) of the matched home-based children (odds ratio, 1.5; 95% confidence interval, 0.7, 3.1). Of 17 center-based children potentially exposed to gastrointestinal illness, 1 (6%) developed subsequent gastrointestinal illness compared with one (6%) of the matched home-based children (odds ratio, 1.0; 95% confidence interval, 0.06, 16.0). Of 12 pairs of children, where the center-based child was potentially exposed to chickenpox while at the center and both were susceptible to chickenpox, 1 center-based child (8%) developed chickenpox compared with 2 home-based children (17%) (odds ratio, 0.5; 95% confidence interval, 0.04, 5.5). We were not able to demonstrate that children who attended the sick child day care center were at significantly increased risk of developing subsequent infections when compared with a matched group of children who did not attend the center.