Corticotropin-releasing factor (CRF) and its receptor subtypes have been implicated in the regulation of endocrine, behavioral and autonomic responses to stress, fear and anxiety. Ovine CRF (oCRF) is a nonspecific CRF receptor agonist that produces anxiogenic-like effects when injected locally into the dorsal aspects of the periaqueductal gray (PAG). This structure is subdivided into four distinct longitudinal columns but their exact functional role is not fully understood. The purpose of the present study was to characterize the effects of oCRF (0.25, 0.5 and 1 microg/0.2 microL) injections into the dorsomedial (dmPAG), dorsolateral (dlPAG) and lateral (lPAG) columns of the PAG using an analysis of the exploratory behavior of rats in the elevated plus-maze (EPM) test. The results showed that microinjections of oCRF intra-dmPAG reduced entries and time spent in the open arms and decreased end-arm exploration and head-dipping. In contrast, oCRF intra-dlPAG or lPAG did not affect the exploratory behavior of the animals in the EPM. These findings point to a columnar specificity for the oCRF effects in the PAG, that is, it increased spatial avoidance measures of the EPM test only in the dmPAG. The proaversive effects of oCRF in the dmPAG gain further relevance when combined with previous immunohistochemical studies showing that CRF-containing projections from the periventricular hypothalamic system arch dorsomedially to the PAG, which could function as an important relay station in the midbrain tectum for avoidance behaviors.