To study the evolution of hemophagocytic syndrome (HPS) in children, we performed a retrospective review of 19 patients (median age, 17.4 months) in whom an infectious diseases consultation was requested at Texas Children's Hospital during the period of September 1991 through September 2001. Clinical findings consistent with HPS most frequently presented during days 6-14 of illness, concomitant with laboratory abnormalities. Fever was present for a median of 19 days before the diagnosis of HPS. Elevated serum lactate dehydrogenase and ferritin levels were noted in all patients. An infectious agent was identified in 42% of patients; 16% were found to have immunologic or vasculitic disease. HPS is a rare but often fatal disease that can initially present as fever of unknown origin with varying clinical findings, and it can be recognized by physicians who are familiar with the evolution of HPS. It is likely that many of these cases remain undiagnosed because of the HPS's rapidly fatal course.