The effect of prostaglandin E2 (PGE2) on the secretion of adrenaline and noradrenaline by the adrenal gland and the interaction between PGE2 and acetylcholine in the adrenal medulla were examined in anaesthetized dogs. In splanchnicotomized dogs, i.v. injection of PGE2 failed to induce any secretion of catecholamines from the adrenal gland, whereas administration of PGE2 into the lumboadrenal artery resulted in a slight, approximately dose-dependent increase in catecholamine secretion within 2 min of the injection. This effect of PGE2 was unaffected by i.v. administration of atropine. Intravenous administration of acetylcholine 1 min after the administration of PGE2 into the lumboadrenal artery of splanchnicotomized atropine-treated dogs had a markedly greater effect on adrenal catecholamine secretion; the resultant output was about twice that evoked by acetylcholine in the absence of PGE2. The effect was more than additive, since the response to acetylcholine was at least one order of magnitude greater than that to PGE2. This indicates that PGE2 and acetycholine may act synergistically in the adrenal medulla.