Recent studies on stress-induced adrenal glucocorticoid secretion have demonstrated quantitatively different effects of individual stress stimuli on hormone release, suggesting that the hypothalamic-pituitary-adrenal axis exhibits discriminative, rather than ubiquitous responses to such challenges, particularly psychological vs. physical stressors. The immediate-early gene, cfos, is expressed by central nervous system neurons in response to numerous physiological stimuli, including stress. The following study investigated whether the distribution and/or intensity of immunolabeling for Fos in the preoptic area and hypothalamus differ after imposition of stressors of variable intensity. Groups of male rats were sacrificed by transcardial perfusion 2 h after (1) transfer to a novel environment (NE stress), (2) confinement within a restraint tube (REST stress), or (3) immobilization (IM) stress. Nonstressed controls remained undisturbed in their home cages. Whereas the NE-stress group exhibited Fos immunoreactivity (ir) only within anterior and lateroanterior hypothalamus, both physical stressors induced immunostaining for Fos in the lateral preoptic area, median preoptic, paraventricular, arcuate, dorsomedial hypothalamic nuclei, and lateral hypothalamus, while numbers of Fos-ir-positive neurons were generally greater in the IM vs. REST stress group. In the IM-stressed rats, additional Fos-ir was observed in the supraoptic and suprachiasmatic nuclei. These studies show that neurons expressing Fos-ir in response to the relatively mild stress of novel environment are distributed differently than those that are transcriptionally activated by more aversive stressors. Findings that Fos-ir occurs in several common sites following exposure to REST or IM stress suggest that local neuron populations may comprise a common neural pathway(s) that is activated by intense forms of stress.