In skeletal muscle fibers, nitric oxide (NO) is produced by neuronal NO synthase (nNOS), which is localised in high concentrations at the sarcolemma. Although nNOS is reported to be involved in many pivotal physiological processes, nNOS knockout-mice do not show any phenotypic malfunctions. We hypothesized that cellular mechanisms exist which compensate for nNOS-deficiency in the knockout- strain. For identification of compensatory mechanisms with biological impact, we searched for proteins with altered expression patterns in extensor digitorum longus muscle (EDL) of nNOS knockout-mice compared to C57/Bl6-wild-type mice by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Of the approximately 450 spots detected on silver-stained 2D-PAGE gels, 10 proteins were differentially expressed. Among these, hemoglobin a and b were significantly down-regulated by 2-3 fold in EDL of nNOS knockout-mice. One protein with Mr of 23.5 kDa and pI of 5.97 was detected in EDL of nNOS knockout-mice but not in C57-mice. This spot was found to be peroxiredoxin-6 by tandem mass spectrometry. Because peroxiredoxin-6 is involved in metabolism of reactive oxygen species we are furthermore investigating the levels of these metabolites in EDL of nNOS knockout-mice.