While sulfur dioxide (SO2) has been previously known for its toxicological effects, it is now known to be produced endogenously in mammals from sulfur-containing amino acid L-cysteine. L-cysteine is catalyzed by cysteine dioxygenase (CDO) to L-cysteinesulfinate, which converts to beta-sulfinylpyruvate through transamination by aspartate aminotransferase (AAT), and finally spontaneously decomposes to pyruvate and SO2. The present study explored endogenous SO2 production, and MT and CDO distribution in different rat tissue. SO2 content was highest in stomach, followed by tissues in the right ventricle, left ventricle, cerebral gray matter, pancreas, lung, cerebral white matter, renal medulla, spleen, renal cortex and liver. AAT activity and AAT1 mRNA expression were highest in the left ventricle, while AAT1 protein expression was highest in the right ventricle. AAT2 and CDO mRNA expressions were both highest in liver tissue. AAT2 protein expression was highest in the renal medulla, but COO protein expression was highest in liver tissue. In all tissues, AAT1 and AAT2 were mainly distributed in the cytoplasm rather than the nucleus. These observed differences among tissues endogenously generating SO2 and associated enzymes are important in implicating the discovery of SO2 as a novel endogenous signaling molecule. (C) 2011 Elsevier Inc. All rights reserved.