A previously healthy 16-yr-old girl was found to have pancytopenia, low reticulocyte count, a cellular bone marrow, and a negative Coombs test, all coincident with clinical and laboratory evidence of infectious mononucleosis. Symptoms and signs of infectious mononucleosis subsided, but pancytopenia and hemolytic anemia persisted. Sucrose hemolysis and acid hemolysis tests supported a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). After 18 mo, the platelet count is normal, but leukopenia and hemolytic anemia continue. The development of PNH in this patient suggests it may have resulted from an effect of infectious mononucleosis.