The purpose of this study is to determine whether hyperthermia-induced hyperventilation with subsequent hypocapnia is relevant to febrile seizures in children. This is only the second study to measure pCO2 and pH values in children with febrile seizures. This prospective case-control study enrolled 18 children who presented with febrile seizures and 18 children who presented with a febrile illness without seizures. Venous blood gas analyses were measured both from the febrile seizure and control group. There was no significant difference in mean blood pH between the febrile seizure and control groups but blood pCO2 was significantly lower in the febrile seizure group. Patients with complex febrile seizures exhibited significantly lower pCO2 levels within 1 hour of seizure onset than patients with simplex febrile seizures. These data indicate that febrile seizures may be associated with hyperventilation and that the ensuing hypocapnia may contribute to the development of febrile seizures.