• A 3-year-old girl, born to an intravenous-drug-dependent mother, had protracted diarrhea, failure to thrive, generalized lymphadenopathy, and recurrent fevers during the first six months of life. At 7 months of age, the Epstein-Barr virus (EBV) genome was detected in her saliva by DNA dot-blot hybridization using a cloned EBV probe. Spontaneous EBV+ lymphoblastoid cell lines had repeatedly developed from her peripheral blood lymphocytes over the subsequent 2½ years. At 11 months of age, persistent tachypnea and a diffuse pulmonary infiltrate developed. Lung biopsy demonstrated a florid, peribronchiolar lymphocytic infiltrate and the EBV genome was identified in the lung tissue. Serum anti-EBV antibodies remained undetectable until 14 months of age. She had a T4+/T8+ ratio of less than 0.8 and serum antibody to human T-cell lymphotropic virus type III. The delayed seroresponse of this patient to symptomatic EBV infection suggests that reliance on EBV serology to diagnose EBV infection in immunocompromised hosts may be inappropriate, and other methods such as DNA probes should be used.