We conducted a matched case-control study to identify risk factors for first febrile seizures, with special emphasis on characteristics of the acute illness episode. Cases were identified through hospital emergency departments; controls were identified through outpatient clinics and emergency departments. Sixty-nine children with first febrile seizures and no history of previous unprovoked seizures were matched for age (+/- 6 months), site of routine pediatric care, and date of visit (+/- 2 weeks) with 1 or 2 febrile controls who had no history of previous febrile or unprovoked seizures. Medical records for the index visit were reviewed, and parents were interviewed by telephone. Illness characteristics examined included height of temperature, type of underlying illness, contact with a physician during the illness but before the index visit, and use of acetaminophen or decongestants. Family history of febrile and of unprovoked seizures, sociodemographic characteristics, daycare use, and selected pre- and perinatal variables were also studied. On multivariable analysis, significant independent risk factors were height of temperature, history of febrile seizures in a first- or in a higher degree relative. Gastroenteritis as the underlying illness had a significant inverse (i.e., protective) association with febrile seizures. Maternal smoking during pregnancy was a marginally significant predictor of febrile seizures.