Ixodes scapularis Say nymphs collected from a natural focus of human granulocytic ehrlichiosis (HGE) in Westchester County, New York, transmitted the HGE agent to uninfected mice in the laboratory. Infection was demonstrated in 3 of 8 mice by polymerase chain reaction analysis of whole blood and microscopic examination of blood smears for morulae. Two of these mice were also positive by xenodiagnosis. Positive xenodiagnostic larvae maintained infection through molting and transferred infection to 1 of 3 mice. Naturally infected I. scapularis ticks transmit the agent of human granulocytic ehrlichiosis to mice, but both acquisition and transmission of this agent by I. scapularis appear to be less efficient than would be expected for Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, the agent of Lyme disease.