A combination of aspirin and acetaminophen was compared to either oral antipyretic agent used alone to reduce fever in children in a controlled clinical study of 60 outpatients and 60 inpatients between the ages of 6 months and 5 years with rectal temperatures greater than 38.9 C (102 F). Temperatures were recorded at one, two, three, four, and six hours after administration of treatment. Results were similar for outpatients and inpatients. The antipyretic combination was generally superior to either drug used alone with average temperature differences reaching statistical significance at many time intervals. Rate and degree of temperature reduction were not greater but were more sustained. Treatment with this combination appears rational in children with high fever when a sustained antipyretic effect is desired. Repeated administration at six-hour intervals lessens the need for more frequent administration of aspirin alone to treat fever.