To explore the association of Epstein-Barr virus infection with childhood pneumonia we studied two patients whose mononucleosis-like illnesses were accompanied by pneumonia; both had virologic and serologic evidence of current or recent EBV infection. We then analyzed the sera of 71 children (age range, 14 months to 9 years) with pulmonary infiltrates for the presence of four classes of antibody to EBV. Antibody responses consistent with current or recent EB virus infection were found in 15. Two children had IgM antibodies to the EBV viral antigen at titers greater than or equal to 1:160, indicating current infection, and all 15 patients had antibody to components of the early antigen complex, suggesting recent infection. A fourfold rise or drop in one or more EBV-specific antibody classes was noted in eight patients within 30 days following onset of clinical illness. Few patients had clinical features suggesting infectious mononucleosis. Eight of the 15 with serologic evidence of current or recent EBV infection also had clinical or serologic evidence of infection with another pathogen--bacterial, viral, or mycoplasmal. Thus, in childhood pneumonia, EBV may be a primary, co-primary, or secondary pathogen; it may be reactivated in the course of infection with another agent, or possibly, by suppressing immune function, it may precipitate infection with some other organism.