Social separation/isolation from either maternal or peer influence can induce a biobehavioral response in rodents and nonhuman primates seeming to mimic certain aspects of human psychopathology. To further explore this paradigm, the effects of 6 weeks of social isolation on electroencephalographic (EEG) recordings and hypothalamic-pituitary-adrenal (HPA) functioning were studied in male and female adult rats. Gender differences were observed in EEG and HPA axis functioning in these rats. Female rats, overall, were found to have higher levels of EEG slow-wave activity over the entire recording period, suggesting more intense levels of slow-wave sleep in those animals. Female rats were also observed to have overall higher plasma corticosterone concentrations and a lower anterior pituitary corticotropin-releasing factor (CRF) receptor density compared with male rats. The male rats, however, showed greater changes in response to social isolation than female rats. EEG power was increased as a result of social isolation in the male animals during the first 30-100 min of the recording. Reductions in the number of CRF receptors were also observed in the brains of the socially isolated rats in several cortical areas; however, again this effect was more prominent in the male animals. These studies suggest that gender is an important variable in determining the biobehavioral response to social isolation.