Muscle wasting is a critical feature of patients afflicted by AIDS, cancer or chronic inflammatory diseases. In a mouse model of muscle wasting, TNF induces oxidative stress and NOS2, and decreases myogenin, Jun-D and creatinine kinase muscle isoform (CKM) expression. Here, we studied 12 patients with muscle wasting due to cancer (N=10) or AIDS (N=2), and 4 control subjects. We show that in skeletal muscle of cachectic patients there is: i] increased expression and activity of the TNF signaling, including TNF mRNA, activation of TNFR1 , and TNF -associated to TNFR1 ; ii] increased oxidative stress, as determined by the presence of malondialdehyde-lysine adducts ; iii] increased NOS2 mRNA and protein ; iv] decreased expression of Jun-D, myogenin, myosin and CKM mRNA and protein ; v] impaired CKM-E box binding activities, associated with decreased JunD/myogenin activities ; vi] oxidative modification and ubiquitination of JunD. These studies show that these molecular pathways are modulated in association with muscle wasting in patients with cancer or AIDS, and whether or not they cause muscle wasting remains to be determined.