The present study attempted to establish whether elevated serum levels of alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) are independent (of each other) markers of systemic inflammation and oxidative stress as assessed by the plasma levels of C-reactive protein (CRP) and lipid peroxides (lipOX), regardless of the presence of underlying metabolic syndrome (as defined by the modified Adult Treatment Panel III (ATPIII) criteria). The plasma levels of CRP and lipOX were determined in 1483 middle-age Japanese men (42+/-9 years). A general linear model analysis indicated that elevated serum ALT and/or serum GGT (levels in the respective highest quartiles) were significantly related to the logarithms of the plasma levels of CRP (Beta=0.08 (0.05-0.11) and 0.08 (0.05-0.11), respectively) and the logarithm of the plasma levels of lipOX (Beta=0.03 (0.01-0.05) and 0.03 (0.01-0.05), respectively), regardless of the presence of underlying metabolic syndrome (MetS) (p<0.01). In addition, the presence of MetS and elevated serum levels of both of these liver enzymes additively increased the plasma levels of CRP and lipOX. Thus, it is proposed that elevated serum ALT and elevated serum GGT are independent markers of the activation of systemic inflammation and increased oxidative stress, independent of their relationship to MetS, and that the presence of MetS and elevations of both of these liver enzymes may additively worsen the atherogenic state.