Heparin-binding EGF-like growth factor (HB-EGF) is a potent mitogen and chemoattractant for diverse cell types including, keratinocytes, fibroblasts and vascular smooth muscle cells. In adult mice, skeletal muscle and endothelial cells prominently express HB-EGF, although analysis of embryonic expression has been limited to studies of heart and kidney development. Here we survey HB-EGF mRNA expression in E7.5-E15 mouse embryos and show that HB-EGF is expressed in branchial arches, limb buds and, transiently, in mature somites between E9.25 and E11. This somitic expression is restricted to the myotomal compartment. Intriguingly, within myotome pairs, the expression of HB-EGF is stronger on the left side of the body, whilst cognate receptors, ErbB1 and ErbB4, are symmetrically expressed in left and right somite pairs. In iv/iv mutant embryos, with inverted left-right body axis, the expression of HB-EGF was also inverted, now being stronger in myotomes on the right side of the body. Thus, the expression of HB-EGF in myotome pairs is regulated by global cues that define the left-right body axis.