Corticotropin-releasing factor (CRF) injected into the cerebral ventricles of small mammals induces EEG limbic seizures, behavioral excitability, stereotyped behavior, and tardive enhancement of hippocampal theta voltage and frequency. Because we addressed this phenomenon when we explained the pathogenesis of infantile spasms in children, we wished to study the interference exerted by some gamma-endorphin fragments on EEG epileptiform and behavioral symptoms induced by CRF in the rabbit. Animals were implanted intracerebroventricularly (i.c.v.) with semichronic cortical and hippocampal electrodes, together with a cannula into the left lateral ventricle. When some gamma-endorphin derivatives (DT gamma E, DE gamma E) were injected intravenously (i.v.) for 4 days (or hydrocortisone once), they prevented the EEG ictal seizures induced in the hippocampus of rabbits by CRF injected i.c.v. Hydrocortisone and DE gamma E also prevented the appearance of scattered spiking and partially prevented tardive enhancement of theta voltage in the hippocampal EEG. Finally, DE gamma E also prevented stereotyped behavior and excitability induced by CRF. These results confirm the regulatory role exerted by CRF in limbic structure excitability and suggest that the above peptides may be involved in a regulatory feedback mechanism of CRF metabolism or activity. The possibility that these peptides may also have interesting antiepileptogenic properties should be considered.