The hypothesis is tested that methionine-enkephalin, a hormone produced in and released from eyestalk of crustaceans, produces hyperglycemia indirectly by stimulating the release of hyperglycemic hormone from the eyestalks. Injection of methionine-enkephalin leads to hyperglycemia and hyperglucosemia in the estuarine crab Scylla serrata in a dose-dependent manner. Decreases in total carbohydrate (TCHO) and glycogen levels of hepatopancreas and muscle with an increase in phosphorylase activity were also observed in intact crabs after methionine-enkephalin injection. Eyestalk ablation depressed hemolymph glucose (19%) and TCHO levels (22%), with an elevation of levels of TCHO and glycogen of hepatopancreas and muscle. Tissue phosphorylase activity decreased significantly during bilateral eyestalk ablation. Administration of methionine-enkephalin into eyestalkless crabs caused no significant alterations in these parameters when compared to eyestalk ablated crabs. These results support the hypothesis that methionine-enkephalin produces hyperglycemia in crustaceans by triggering release of hyperglycemic hormone from the eyestalks.