A "closed space" subarachnoid hemorrhage (SAH) was produced experimentally in cats by rupture of the right middle cerebral artery to test the working hypothesis that a stressful event which provokes powerful sympathoadrenal discharge: causes a massive release of co-stored endogenous enkephalins together with catecholamines, induces an increased rate of opioid peptide precursor processing and/or synthesis, and eventually results in markedly elevated tissue levels of enkephalins relative to controls and to co-stored catecholamines. Adrenal medulla and other tissues were analyzed for met- and leu-enkephalins by RIAs and norepinephrine and epinephrine by HPLC-EC at 4 hrs, 3, 10, 16 and 30 days post-SAH. Catecholamines of adrenal medulla were already decreased at 4 hrs and by 3 days post-SAH depletion of epinephrine reached 86% and norepinephrine 53% compared to controls. Concurrently, at 4 hrs and 3 days post-SAH, the adrenal medulla was depleted 47% of met- and 53% of leu-enkephalins. By 10 days post-SAH, when catecholamines had regained control levels, met-enkephalin was elevated to 240% of control and 435% compared to the 3 day depletion; it remained elevated through 30 days post-SAH. In comparison, after 10 days reserpine treatment when catecholamines were markedly depleted, met-enkephalin rose to 970% and leu-enkephalin to 360% relative to controls, confirming recent reports in the literature. The data suggest that release of enkephalins originates primarily from epinephrine-type cells of the adrenal medulla in cat.