The importance of adenovirus in initiating respiratory disease in young children is stressed in this report. The incidence, clinical illness, asymptomatic carriage, and serologic response of acute adenovirus-associated infection are described in a carefully followed cohort of normal children cultured with each episode of febrile respiratory illness. During a 6-year period, 8.2% of 1,416 nasal washings obtained from sick infants and children less than 7 years of age yielded adenovirus. Adenoviruses were isolated from only 1/174 (0.6%) cultures taken from well children. Typing of 98 isolates showed 81% to be types 1 or 2. A ≥ fourfold rise in neutralizing titer was seen in 45/59 (76%) sampled. In a subset of the cohort observed for 2-week periods in a day care setting, 14 of 21 well children (67%) exposed to symptomatic children with adenovirus infection developed febrile respiratory symptoms and shedding of the same serotype within 2 weeks of exposure. This study confirms that adenovirus has a high attack rate and causes significant respiratory disease in young children.