Febrile seizures can be the first sign of epilepsy. In a recent study, patients with temporal lobe epilepsy were reported to carry the interleukin-1beta allele 2 at position -511 more often than healthy control subjects. Because pro-inflammatory cytokines, such as interleukin-1, are well-known inducers of fever and therefore could play an important part in the pathogenesis of febrile seizures, we have, in this study, analyzed the cytokine gene polymorphism of interleukin-1beta at position -511 in children with febrile seizures and control subjects. We found a statistically significant increase in the frequency and the carriage of interleukin-1beta (-511) allele 2 in children with febrile seizures (n = 35) compared with healthy blood donors (n = 400) (P = 0.03 and P = 0.05, respectively). In previous studies, this allele has been connected to increased in vitro production of interleukin-1. Children with febrile seizures may therefore have an increased pro-inflammatory reaction during fever. This pro-inflammatory reaction may also predispose some children to the development of epilepsy.