Recent data from various laboratories suggest that the activation of endogenous corticotropin-releasing factor (CRF) may contribute to the behavioral and neuroendocrine effects of cocaine. In the present study, the time-dependent variations in CRF-like immunoreactivity (CRF-LI) in the hypothalamus and several extrahypothalamic brain regions were determined after acute cocaine administration to handled rats. The intraperitoneal injection of 7.5 mg/kg cocaine led to a significantly decreased CRF-LI level in the basal forebrain and to a significantly increased CRF-LI level in the amygdala 60 min after administration, while the CRF-LI content was decreased in the hypothalamus and in the hippocampus 180 min after cocaine treatment. These results suggest that the durations of the effects of cocaine on CRF-LI are in the brain region-specific, which might contribute to the mediation of the diverse behavioral and neuroendocrine effects of cocaine.