Trauma and blood transfusion led to profound, persistent infectious mononucleosis in a 21 year old man. Splenectomy and trauma had apparently produced transient immune deficiency which was complicated by osteomyelitis of a fractured tibia. The transfused blood probably contained Epstein-Barr virus (EBV). Infectious mononucleosis had ensued 25 days after a blood transfusion was given, antibodies to EBV appeared in his serum, and the infectious mononucleosis persisted for nearly two years. His immunity returned gradually to normal, but because of nonunion of the fracture site, which was infected by Staphylococcus aureus, above-knee amputation was required. The acquired, transient immune deficiency to EBV and profound infectious mononucleosis seen in this patient is analogous to inherited, permanent immune deficiency to this virus in the X-linked lymphoproliferative syndrome.