Over 260 cases of human ehrlichiosis have been identified in the United States since 1986. A causative agent was recently isolated from a patient and designated Ehrlichia chaffeensis because of serologic and genotypic differences from Ehrlichia canis. Ehrlichia species are obligate intracellular bacteria that infect hematopoietic cells. Human ehrlichiosis is characteristically a systemic febrile illness with headache, myalgias, and frequent gastrointestinal symptoms associated with leukopenia, thrombocytopenia, and mild to moderate hepatic injury following a recent tick exposure. The pathologic findings in several cases suggest that the major pathophysiologic abnormality results from generalized infection of reticuloendothelial cells and peripheral sequestration of leukocytes and platelets. Tetracycline appears to be an effective therapy. The diagnosis depends upon seroconversion to E. chaffeensis in convalescence. Early diagnosis requires clinical suspicion and is probably important for minimizing morbidity that results from delayed diagnosis.