Effects of 1.0 mg/kg and 0.4 mg/kg intraperitoneal nicotine on hypothalamic and extra hypothalamic levels of corticotropin releasing factor (CRF) were examined in 104 rats. CRF, a 41-amino acid peptide involved in responses to stress, fear and anxiety, influences the same neurotransmitter systems as nicotine, a psychoactive component of tobacco. Radioimmunoassays revealed that in macro-dissected hypothalami, 15 minutes treatment with 1.0 mg/kg nicotine significantly increased CRF content compared to no treatment. The 1.0 mg/kg dose did not elicit effects in macro-dissected amygdala and brain stem. With 0.4 mg/kg nicotine, no significant effects were observed in micro-dissected hypothalamic paraventricular nucleus, amygdaloid and brain stem nuclei. As expected, plasma corticosterone levels were significantly increased with both doses of nicotine. Overall, no clear cut effects of nicotine on CRF were observed. Micro-dissection studies on specific nuclei using varying doses and time points would help elucidate interactions of nicotine with CRF systems