The substance P/neurotachykinin-1 (NK-1) and the mu-opioid G protein-coupled receptor systems endow brainstem respiratory regions and display discrete developmental patterns. Hypoxia-induced neuropeptide release may increase receptor endocytosis, reducing receptor accessibility to ligands. We wondered whether the attenuated respiratory response to hypoxia of developing piglets after single (Respir. Physiol. 92 (1993a) 115) or repeated daily hypoxic exposure (J. Appl. Physiol. 83 (1997) 522) is influenced by differential endocytosis of NK-1 vs mu-opioid receptors. Whereas the long-term (24 h) response of both receptors to recurrent hypoxia in piglet brainstem is similar, i.e. upregulation, the short-term (5 min) response to single or recurrent hypoxia, albeit in rats, is different: radiolabelled NK-1 receptors are greatly reduced, suggesting enhanced endocytosis, but mu-opioid receptors remain unchanged, implying unaltered endocytosis. If confirmed in piglet brainstem, this difference would produce relatively more available mu-opioid receptors to opioid peptides in hypoxia that might contribute to the attenuated respiratory responses to single and repeated hypoxia during development.