The meridian system is the central theory and guiding principle for therapies related to mind-body interactions such as acupuncture, Qi Gong and meditation. Investigators have demonstrated in both humans and animals that acupoints/meridians possess characteristics of low electric resistance. We have found that nitric oxide (NO) contents and neuronal NO synthase expressions are consistently increased in three meridian skin regions in rats. Our recent studies reveal that NO contents are increased over PC 4 to 7 containing 4 acupoints and tended to increase in BL 56 to 57 along the region with two acupoints compared to nonmeridian control in humans. Consistent with the postulated role of nonenzymatic NO generation, enhanced NO levels in the acupoints/meridians are reduced by using sodium hypochlorite to reduce bacteria on skin surface. Furthermore, preliminary data show that NO contents are increased over PC acupoints and meridian during meditation practice. I hypothesize that 1) Nonenzymatic NO production and neuronal NO synthesis contribute to enhanced NO generation in acupoint/meridians; and 2) Meridian practices induce NO generation which mediates chemical-electrical activity for the biophysical characteristics of acupoints/meridians. In view of the critical importance and unexplored territory of the meridian system, our major aims are: 1) Define whether local NO levels (NOx- concentrations) are selectively increased in the acupoints and/or in the meridian regions; 2) Determine if nonenzymatic NO generation and/or neuronal NO synthesis contribute to enhanced NO levels in acupoints/meridians; 3) Identify if electrical and temperature stimulation induces NO production in acupoints/meridians paralleled to low electrical resistance; 4) Examine whether acupuncture induces NO production/release along dual directions of meridian pathways; and 5) Investigate whether Qi Gong and/or meditation practices predominantly increase NO generation in the acupoints and meridians. Quantification of NO metabolites collected from the skin surface of acupoints and meridian lines with a special device will be integrated with physiological/pharmacological manipulations during meridian practices to test the hypotheses in humans. The results should advance our understanding of the roles of endogenous NO generation/release in responses to acupuncture, Qi Gong and meditation practices m the acupoints/meridians, and yield new insights regarding the effects of non-enzymatic NO generation and neuronal NO synthesis on chemical-electrical activity of the low skin resistance function of meridians.