Natural genetic variation is the raw material of evolution and influences disease development and progression. To analyze the effect of the genetic background on protein expression in the nematode C. elegans (Caenorhabditis elegans), the two genetically highly divergent wild-type strains N2 (Bristol) and CB4856 (Hawaii) were compared quantitatively. In total, we quantified 3,238 unique proteins in three independent SILAC (stable isotope labeling by amino acids in cell culture) experiments. The differentially expressed proteins were enriched for genes that function in insulin-signaling and stress response pathways.