Met-enkephalin circulates in several forms, some of which may be derived from proteins other than proenkephalin A, and plasma levels of both free native, and peptidase-derivable Met-enkephalin are modulated physiologically. Met-enkephalin also functions as a growth factor on many cell types at a receptor that is distinct from the neuronal opioid receptors. Enhancement of immune system function is mediated through met-enkephalin receptors on leukocytes.