We previously showed that the adrenocorticotropin hormone (ACTH) is a mitogen for myoblasts and is present in post-implantation mammalian embryos (Cossu et al. [1989] Dev. Biol. 131:331-336; De Angelis et al. [1992] Dev. Biol. 151:446-458). In this paper, we investigated the expression of the corresponding gene, pro-opiomelanocortin (POMC), by in situ hybridization and polymerase chain reaction. In situ analysis revealed low level expression in the basal layer of 10.5 d.p.c. neural tube and in several discrete areas around the dorsal aorta. By more sensitive Reverse-transcription polymerase chain reaction (RT-PCR) analysis, expression was detected also in developing limb buds and in cultured myogenic cells, but not in fibroblasts. To investigate the possible role of POMC gene expression in myogenesis, we induced its over-expression in proliferating myoblasts. Upon sub-optimal growth conditions, over-expressing cells were found to give rise to clones larger than control cells. The differentiation potential of POMC over-expressing myogenic cells was unchanged.