The corticotropin releasing hormone (CRH) system has been suggested to initiate seizure activity in the developing brain. However, human data to support this theory is lacking. In this study, we have demonstrated that the expression of CRH, CRH-binding protein, and CRH-R1 (a CRH membrane receptor) were significantly elevated in cortical tissue obtained from 6 children with generalized epilepsy (mean age 8.2 ± 1.5 years) relative to age-matched controls (mean age 7.8 ± 1.4 years). In contrast, no significant difference in the expression of CRH-R2 was observed. The advent of CRH-R1 receptor antagonists may prove useful as novel anticonvulsants.