I.c.v. injection of L-ornithine has been shown to have sedative and hypnotic effects on neonatal chicks exposed to acute stressful conditions. To clarify the mechanism, we conducted three experiments under strengthened stressful conditions with corticotropin-releasing factor (CRF). In Experiment 1, the effect of i.c.v. injection of CRF, L-ornithine (0.5 μmol) or CRF with L-ornithine on the stressful response of chicks was investigated. Compared with the vehicle control, CRF increased distress vocalizations and the time spent in active wakefulness. L-Ornithine increased the time spent in sleeping posture, even following stimulation with CRF. In Experiment 2, dose-dependent effects of L-ornithine were investigated using i.c.v. administration with vehicle, CRF alone or CRF plus L-ornithine (0.125, 0.25 or 0.5 μmol). L-Ornithine decreased the CRF-stimulated distress vocalizations in a dose-dependent manner. In Experiment 3, the chicks were injected i.c.v. with either CRF, CRF plus L-ornithine (0.5 μmol), CRF plus the Y-aminobutyric acid (GABA)_A receptor antagonist picrotoxin or L-ornithine with picrotoxin. The sedative and hypnotic effects induced by L-ornithine were blocked with co-administration of picrotoxin. These results suggest that L-ornithine could attenuate CRF-stimulated stress behaviors acting at GABA_A receptors.