Stable isotope labeling by amino acids in cell culture (SILAC) has become a powerful tool for quantitative proteomics. Recently, this approach has been extended to living organisms, including yeast, flies, fish and rodents. For example, the SILAC-mouse is completely labeled with the stable isotope 13C6 lysine (Lys6). Mass spectrometric analysis of incorporation levels of brain and heart tissue allowed for the determination of more than 3000 protein turnover rates. Proteins derived from fully labeled mice were used as a “spike-in” standard to quantify relative changes between two proteomes. We used the SILAC mice technology to map quantitative proteomic changes of knock-out mice and for the comparison of different tissues such as slow and fast muscle fibers. The SILAC-mouse approach is a simple method to compare proteomes from living animals and thereby determine global protein changes under complex in vivo conditions