Complex traits, including common disease-related traits, are affected by many different genes that function in multiple pathways and networks. Many of the signalling pathways involved in these traits are conserved among species and also present in the nematode C. elegans. To study the effect of natural genetic variation on the abundance of proteins involved in signalling pathways, we used selected reaction monitoring and quantitative trait loci mapping to analyse proteins from four pathways (apoptosis, MAPK, Notch and Wnt) in recombinant inbred lines (RILs) generated from the two genetically divergent C. elegans wild-type strains Bristol N2 and Hawaii CB4856.