We reviewed 19 cases of hepatosplenic cat-scratch disease at Texas Children's Hospital (Houston). The range of the patients' ages was 2 years 4 months to 11 years 8 months. The chief complaint was fever for all patients. The duration of fever before diagnosis was 7 to 56 days (mean, 22 days). Abdominal pain was present in 13 patients (68%). Thirteen children were treated with rifampin alone, and three received rifampin therapy plus gentamicin or trimethoprim-sulfamethoxazole. Once rifampin therapy was initiated alone or in combination, improvement was noted within 1 to 5 days (mean, 2.6 days) for patients who had had prolonged fever the duration of which before rifampin therapy averaged 3 weeks. The most common dosage and duration for our patients were 20 mg/[kg x d] every 12 hours and 14 days, respectively. Rifampin should be considered in the initial antimicrobial treatment of hepatosplenic cat-scratch disease.