We present 2 atypical cases of babesiosis and a review of babesiosis. The first patient was a 72-year-old man with an intact spleen, who had marked intravascular hemolysis. His RBCs were parasitized heavily with trophozoites of Babesia, and he had a large number of extracellular aggregates of Babesia. The infection did not respond to oral antibiotic therapy, and he required an RBC exchange transfusion. The second patient was a 29-year-old man who had undergone splenectomy and who had multiple episodes of fever and gastrointestinal symptoms for 4 months, with partial response to antibiotics. Thin smears revealed both intraerythrocytic and extraerythrocytic forms in very low numbers. The infection responded promptly to clindamycin and quinine therapy. The varying clinical manifestations, from acute to chronic, at a wide range of ages and often the difficulty of detection by routine blood smears make it necessary that a high index of clinical suspicion be present for prompt diagnosis. With increasing numbers of cases of transfusion-transmitted babesiosis being reported, protection of the blood supply is essential.