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<h3>Objective.</h3> —To characterize the clinical presentation and course, laboratory findings, and treatment outcome of 12 patients with human granulocytic ehrlichiosis. <h3>Setting.</h3> —The 12 patients were male, ranged in age from 29 to 91 years, and contracted their illness in Wisconsin or Minnesota. <h3>Methods.</h3> —Cases were recognized by the presence of intracytoplasmic inclusions (morulae) in peripheral neutrophils of patients presenting with temperature of 38.5°C or higher, chills, severe headache, and myalgias. All patients had a complete blood cell count and blood chemistry profile. Blood smears were examined by light microscopy. All available paired serum samples were analyzed for presence of indirect fluorescent antibodies against<i>Ehrlichia chaffeensis, Ehrlichia phagocytophila</i>, and<i>Ehrlichia equi</i>. Blood samples from 12 patients were subjected to polymerase chain reaction analysis using primers specific for the<i>E phagocytophila/E equi</i>group, primers that include the agent identified in our patients, as well as<i>E chaffeensis</i>. <h3>Results.</h3> —Varying combinations of leukopenia, anemia, and thrombocytopenia were found in all but one patient. All 12 patients demonstrated morulae in the cytoplasm of neutrophils, but not in mononuclear white blood cells. Serum assays failed to detect antibodies against<i>E chaffeensis</i>, but eight of 10 patients and seven of 10 patients tested had antibody titers of 1:80 or more for<i>E phagocytophila</i>and<i>E equi</i>, respectively. Polymerase chain reaction products obtained with primers for<i>E phagocytophila, E equi</i>, and the granulocytotropic<i>Ehrlichia</i>revealed that seven patients were infected with the same agent. The results of serological assays or polymerase chain reaction strongly suggest that all 12 patients were infected by<i>E phagocytophila, E equi</i>, or a closely related<i>Ehrlichia</i>species. Two of the 12 patients died. The other 10 patients improved rapidly with oral doxycycline treatment. <h3>Conclusions.</h3> —We believe that all 12 patients have been infected with a granulocytic<i>Ehrlichia</i>species, reflecting a recently described new disease entity. The infective organism appears to be closely related to<i>E phagocytophila</i>and<i>E equi</i>. The geographic domain of human granulocytic ehrlichiosis is currently unknown. This novel granulocytic<i>Ehrlichia</i>species is capable of causing fatal infections in humans. Early detection and treatment with tetracycline drugs appear to offer the best chance for complete recovery. (<i>JAMA</i>. 1994;272:212-218)