Potential anxiogenic-like properties of urocortin, a corticotropin-releasing factor (CRF)-related neuropeptide, were investigated in models of anxiety in rodents. In the elevated plus-maze, CRF- and urocortin-treated rats (0.1 nmol, i.c.v.) spent less time and made fewer entries into open arms. In the light-dark test in mice, urocortin (0.006-0.06 nmol, i.c.v.) dose-dependently reduced time and number of transitions into the lit area. Urocortin also dose-dependently (0.02-0.2 nmol, i.c.v.) reduced mice exploratory behaviour in an open field. This effect was reversed by diazepam (0.1-1 mg/kg, i.p) and by the CRF receptor antagonist alpha-helical CRF (0.8-8 nmole, i.c.v.). These data show that urocortin produces anxiety-like effects in several behavioural paradigms in rodents.