We recently reported that stress alters interleukin (IL)-6 and IL-6 receptor (IL-6R) mRNA levels in the hypothalamus. Odorants are reported to exert anti-stress effects. The aim of our study was to determine the effects of odorants on IL-6 and IL-6R mRNA expression in the hypothalamus, using reverse transcriptase-polymerase chain reaction and on serum levels of adrenocorticotropic hormone (ACTH) and corticosterone in rats exposed to stress. Control rats were not exposed to stress; test control rats were exposed to 4 h stress then immediately killed. In other groups, rats were exposed to the same stress followed by 30 min exposure air, dimethoxymethylbenzene (DMMB), or citralva. In the air group, IL-6 and IL-6R mRNA levels were significantly reduced and serum levels of ACTH and corticosterone significantly increased relative to the control. Exposure to DMMB significantly augmented IL-6 mRNA expression but restored that of IL-6R mRNA, did not change serum corticosterone level relative to that of the air group and significantly reduced ACTH. In comparison, citralva restored the expression of IL-6 and IL-6R mRNAs and significantly increased serum ACTH and corticosterone levels. Our results indicate that citralva enhances stress-induced activation of the hypothalamic-pituitary-adrenal axis by corticotropin-releasing hormone (CRH)-mediated stimulation of IL-6, while DMMB enhances the beneficial action of IL-6 without affecting CRH.