The development of proopiomelanocortin (POMC) derived peptides was compared to that of leucine-enkephalin ([Leu]ENK) and dynorphin A (DYN-A) immunoreactivity (i.r.) in the rat CNS and pituitary gland. POMC i.r. appeared first in hypothalamic neurons on embryonic day E12, in pituitary anterior lobe (AL) cells on E15, in pituitary intermediate lobe (IL) cells on E16, and in perikarya of the nucleus tractus solitarius on E17. In the fetal stages (E19-22), all POMC systems appeared adult-like; however, peak i.r. occurred between postnatal days P21-28. The development of alpha-MSH (a-MSH) i.r. was dissimilar to that of other POMC peptides including beta-endorphin (B-End). In contrast, both [Leu]ENK and DYN-A i.r. appeared in later embryonic stages (E16-17), and their maturation lagged behind that of POMC peptides. Peak i.r. for these latter peptides also occurred between P21-28.