Human ehrlichiosis is a recently described illness that is thought to be tick-borne. Most recognized cases of human ehrlichiosis manifest as an acute nonspecific febrile illness. The natural history of untreated symptomatic disease is largely unknown. Over a 4-year period, we identified 41 cases of human ehrlichiosis by serological testing, polymerase chain reaction analysis, or both methods. The principal finding for six of the patients was protracted fever. The duration of their fevers ranged from 17 to 51 days. At the time of presentation, all six patients had clinical features, laboratory features, or both consistent with a diagnosis of ehrlichiosis. Polymerase chain reaction analysis helped to rapidly confirm the diagnosis for four of five patients tested. The diagnosis of human ehrlichiosis should be considered for patients with prolonged fever who live in an area of endemicity.