To examine the effects of subchronic exposure of low concentrations of toluene on the hypothalamo-pituitary-adrenal gland (HPA) axis, we analyzed the corticotropin releasing hormone (CRH) neurons in the hypothalamus and the adrenocorticotropic hormone (ACTH) cells in the pituitary gland of female mice, which inhaled toluene during 3 month period and were sensitized with ovalbumin (OVA). The data was culled using the immunocytochemical, morphometrical and RT PCR methods. Adult female mice were divided into non allergy and allergy groups, which were sensitized with OVA. Each subgroup was further subdivided into control and 50 ppm toluene exposure subgroups. The number of CRH-immunoreactive (ir) neurons and ACTH-ir cells, and ACTH-mRNA expression, were significantly elevated by toluene inhalation and OVA sensitization. Our results suggest that low concentrations of toluene and OVA sensitization act on the HPA axis as stressors.