In a prospective study over 7 years, 105 consecutive pediatric patients with hyperpyrexia (temperature > or = 41.1 degrees C [106 degrees F]) were evaluated to determine the incidence, sensitive indicators, and types of illnesses encountered. The incidence of hyperpyrexia in a large urban pediatric emergency department was 0.36 per 1,000 visits or approximately one in 2,759 visits. In patients with temperature > or = 41.1 degrees C, 65 (61.9%) had a serious illness. Pneumonia (33 lobar, three interstitial, two clinical) was the most common diagnosis (36.2%), followed by probable viral illness in 20 (19.0%) of the patients. Bacteremia (6.7%) and bacterial meningitis (5.7%) were less commonly found. Four (3.8%) patients died. The admission rate was 62.9%. Eighteen patients (17.1%) also had seizures. Sensitive indicators to help distinguish those with serious illness, with the exception of clinical appearance, were not found. Pneumonia is commonly found in children with hyperpyrexia. Temperature > or = 41.1 degrees C was associated with a high rate of serious disease.