In a prospective study of 104 infants between 1 and 3 months of age hospitalized with pneumonitis, 65 (63%) had evidence of infection with one or more potential respiratory pathogens. Single infections were noted in 48 (74%) whereas mixed infections occurred in 17 (26%) of 65 infected infants. The four most common infections were Chlamydia trachomatis (15/59, 25%), Ureaplasma urealyticum (8/38, 21%), cytomegalovirus (21/104, 20%), and Pneumocystis carinii (19/104, 18%). In sharp contrast, the incidence of these infections in control infants was 0% (0/25), 4% (2/49), 3% (3/97), and 0% (0/64), respectively. The clinical, radiologic, and laboratory characteristics of the pneumonitis syndrome associated with Chlamydia, cytomegalovirus, and Pneumocystis were indistinguishable from each other. Patients with mixed infections had a more severe pneumonitis as measured by the occurrence of apnea and the need of oxygen therapy and mechanical ventilation. The patients enrolled in this study are being followed-up to determine the longitudinal course of these infections.