To describe a case of human babesiosis and review the literature on the disease.We describe a 62-year-old man with babesiosis, outline his clinical course and response to therapy, and discuss the use of the polymerase chain reaction for the diagnosis and monitoring of the infection.The onset of the disease was insidious, with fatigue, fever, weight loss, intermittently discolored urine, and anemia. Computed tomography of the abdomen revealed a small, shrunken spleen with an irregular border. With treatment, the symptoms gradually resolved. Although peripheral blood smears were negative soon after therapy, Babesia microti DNA was detected by polymerase chain reaction 53 days after initial examination.The development of improved methods for diagnosis, including indirect immunofluorescent antibody assays and the polymerase chain reaction, provides more sensitive detection of the parasitemia associated with babesiosis. Use of these methods may help to delineate the complete clinical spectrum of this infection and its geographic distribution in the United States.