In 1988, the Centers for Disease Control and the Oklahoma State Department of Health identified 40 patients who had a fourfold or greater change in antibody titer in response to Ehrlichia canis. The median age of these patients was 42 years, 83% were male, 76% became ill between May and July, and 92% reported recent exposures to ticks. Patients resided in or were exposed to ticks in 14 states, including five where ehrlichiosis had not been reported before 1988. Thirty-four patients (85%) were hospitalized, and many had serious complications, including acute respiratory failure (seven patients), encephalopathy (six patients), and acute renal failure (four patients). Pulmonary infiltrates were demonstrated in 14 patients, cerebrospinal fluid pleocytosis was seen in 10 patients, and elevated levels of serum creatinine were demonstrated in eight patients. Two patients, both of whom had preexisting medical problems, died. Nonhospitalized patients received tetracycline therapy earlier in the course of their illness than hospitalized patients. There was no significant difference in the interval from initiation of antibiotic therapy to the first day of defervescence between patients treated with tetracyclines and those treated with chloramphenicol.