The postnatal development of somatostatin [SOM]- and neuropeptide Y[NPY]- immunoreactive[ir] neurons were examined in rat cerebral cortex considering their coexistence in cortical neurons. Using double immunohistochemical staining for SOM and NPY with diaminobenzidine and benzidine dihydrochloride as chromogens, we subdivided immunoreactive cells into double-labeled SOM/NPY-, SOM only-, and NPY only-ir neurons. Interestingly, SOM/NPY- and SOM only-ir neurons were detectable even at the day of birth, in contrast to NPY only-ir cells which first appeared in most cortices from two weeks of age. The morphological features of double-labeled SOM/NPY neurons were not identical to those SOM only- and NPY only-ir neurons. No apparent changes in the shape and size of single-labeled neurone occurred with age ; throughout their postnatal life they were round and ovoid, had a thin rim of perinuclear cytoplasm, and short processes. In contrast, the features of SOM/NPY-ir neurons were not consistent during postnatal life. By day P7, these neurons showed immature features ; they began to show more advanced neuronal characteristics by week P2, when they had a larger and more intensely-stained cytoplasm. In addition, their processes were longer, thicker and more complex than at earlier ages. At this age, SOM/NPY-ir somata were close to their maximum size. From week P4, they became smaller and were lightly labeled. SOM/NPY-ir somata were larger than SOM only- and NPY only-ir somata at and after two weeks of age. The present results showing different postnatal maturation patterns such as time of appearance and morphological features suggest that double-labeled SOM/NPY and single-labeled neurons might be different populations regulated by different mechanisms in their development, and with different functional properties during development.