Stress exacerbates allergic disorders such as atopic dermatitis and asthma. It is also an important factor affecting blood flow (BF). Allergic reactions also affect blood flow. For example, we observed that mice sensitized with hen egg-white lysozyme (HEL) have decreased BF during the allergy induction phase. Based on this finding, we established a model for evaluating chronic restraint stress-enhanced allergies. Mice were sensitized with 12.5 µg/head of HEL on day 0, then restrained for 90 min daily on days 1-3, 5, and 6 in a modified 50 mL polystyrene conical centrifuge tube with multiple air holes for ventilation. We used the decrease in BF during that time as a guide for developing an in vivo assay for substances that can inhibit stress-enhanced allergies. Finally, we demonstrated the utility of the new method by testing crude drugs that are used solely or in combination with other crude drugs to treat stress-related illness and neuropsychiatric symptoms. Our model should be useful for identifying potential anti-stress-enhanced allergy drugs.Key words allergy; chronic restraint stress; blood flow; crude drug; egg-white lysozyme Allergic diseases, such as atopic dermatitis and asthma, become severe or relapse due to stress. However, there have been no systems that can evaluate allergy enforced by stress.As stress is an important factor affecting blood flow (BF), we have developed a new assay system based upon our findings 1-3) on BF decrease in the induction phase of allergy in the tail vein of mice sensitized by use of hen egg-white lysozyme (HEL). We previously developed an in vivo assay to search natural resources for allergy-preventive substances. We used it to assess BF during the allergy induction phase in the tail veins of mice that have been sensitized to HEL. 1-3) Blood flow in the model appears to be regulated by various factors such as nitric oxide, thromboxane A 2 (TXA 2 ), prostacyclin (PGI 2 ), and endothelin-1 (ET-1) together with cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and constitutive nitric oxide synthase (cNOS). 1) A reduction of BF occurs via two pathways. One is an iNOS-independent response involving TXA 2 and ET-1; and the other is an iNOS-dependent response involving cyclooxygenase COX-1, COX-2, and PGI 2 . 2) Its clinical condition is also similar to the "oketsu" (the state of blood stagnation) of the Kampo medicine (a traditional medicine practiced in Japan, based on ancient Chinese medicine). 3) In our continuing search for allergy-preventive substances from natural sources using this assay method. [4][5][6][7] On the other hand, allergic disorders become severe or relapse due to stress. 8,9) It also affects the production of substances such as interleukin and tumor necrosis factor, which cause allergies and inflammation. 10) Additionally, stress is an important factor affecting BF. 11-13) However, assay for compounds that inhibit stress-enhanced allergy have been unavailable. Therefore, we developed a novel assay system based upon ...