Peptides related to alpha-MSH (collectively termed melanocortins) stimulate nerve growth following injury and may play a physiological role in the repair process. Melanocortins are not normally present in mature peripheral nerves but MSH-like bioactivity has been observed in extracts of injured nerves. alpha-MSH could derive from reexpression of the POMC prohormone in injured nerves or from proteolysis of the intermediate-size neurofilament protein that bears antigenic similarities to melanocortins. Using a radioimmunoassay that will distinguish between alpha-MSH and neurofilament-derived fragments, we have shown that alpha-MSH is not present (detection limit 74 pg alpha-MSH/mg protein) in damaged rat sciatic nerves.