Glutamate decarboxylase (GAD) catalyzes the synthesis of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, from glutamate. An expression of GAD protein has been reported for brain and pancreas, but not for skin. In this study, we present evidence that GAD67 mRNA and protein are expressed in mouse skin and in human dermal fibroblasts. The expression of GAD67 gene is weaker in aged mouse than the young one. To further explore the function of GAD in skin, we have examined a potential role(s) of GABA in human dermal fibroblasts. We have observed that GABA stimulates the synthesis of hyaluronic acid (HA) and enhances the survival rate of the dermal fibroblasts when fibroblasts are exposed to H(2)O(2) an oxidative stress agent. Also observed were lowering the levels of HA and collagen in the embryonic skin from GAD67 deficient mouse as compared to those from the wild-type (WT) mouse. In this study, we have presented the evidences that GAD67 is localized in the dermis and is potentially involved in variety of skin activities.