The participation of the medullary structures in the total respiratory effect of opiates was studied by restricting the access of the delta-agonist D-ala2-D-leu5-enkephalin and the mu-agonist D-ala2-Me-Phe4-Met (O) ol5-enkephalin, to the ventral medullary surface, and by comparing their responses with those induced after i.c.v. administration. The medullary structures were more resistant to the overall depressant action. The opioids in the medulla depressed preferentially the tidal volume and the CO2-responsivity whereas the i.c.v. injections affected severely the frequency. No qualitative differences were found between the effects of the delta- and mu-agonist. It is concluded that both, medullary and supramedullary structures are involved in the respiratory response to opiates, but they participate with unique functions in the overall respiratory effect.