The effect of hypoxia on plasma met-enkephalin and catecholamine levels was studied in chronically catheterized fetal sheep. Maternal and fetal hypoxia was maintained for 20 min. We found hypoxia significantly increased the plasma levels of large mol wt met-enkephalin containing peptides from 1755 ± 229 pg/mL during baseline to 4408 ± 1426 pg/mL by 15 minutes of hypoxia. The levels of the met-enkephalin pentapeptide were unchanged during hypoxia from a baseline value of 168 ± 56 pg/mL. Norepinephrine and epinephrine levels increased 5- and 10-fold, respectively, by 15 min of hypoxia. These observations suggest cosecretion of the large mol wt met-enkephalin peptides with catecholamines during stress in developing animals.