Interleukin-1 gene family: interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1RA) has been suggested to play a pathogenic role as an important mediator of epileptic seizure. In experimental models it has been reported that intracerebral application of IL-1β enhances epileptic activity while IL-1RA mediates anticonvulsant actions. In this study we analyzed serum and cerebrospinal fluid (CSF) levels of IL-1β and IL-1RA in 14 patients with age-dependent epileptic encephalopathy (ADEE), including: West syndrome (n = 11), early infantile epileptic encephalopathy with suppression-burst (n = 2), and malignant migrating partial seizures in infancy (n = 1). On comparison between pre- and post-improvement of symptom and EEG findings, serum IL-1RA levels post- (413.2±165.5 pg/ml) were significantly higher than those of pre- (251.5±125.4 pg/ml) improvement. Serum IL-1β levels (11–12 pg/ml) barely increased in three patients pre-improvement, and these levels decreased to be below detectable levels in all patients post-improvement. On comparison between recurrent and non-recurrent seizure groups regarding serum IL-1RA levels pre-improvement, the levels in the recurrent seizure group (212.8±139.0 pg/ml, n = 9) were lower than those in the non-recurrent seizure group (287.0±117.1 pg/ml, n = 5), but the difference was not significant. There was no difference in CSF IL-1RA levels between recurrent and non-recurrent seizure groups (137.3±69.7 vs. 134.6±63.6 pg/ml, respectively). CSF IL-1β levels were below detectable levels in all except for one patient (31.2 pg/ml). In conclusion, the serum IL-1RA level provided a basis for determining the effectiveness of treatment, and may become a valid predictive marker of ADEE severity.