We have found evidence that histamine stimulates secretion in the in vitro rabbit pancreas. The observations have been extended to the isolated pancreatic lobule preparation in rabbit. Histamine produces a significant stimulation of amylase and protein secretion at 10 to the minus 5th power M with ED50 being about 3 x 10 to the minus 5th power M and the maximal response occurring at 10 to the minus 3rd power M. The stimulation is approximately one-third that of cholecystokinin and is inhibited by the histamine antagonist (H-1) mephyramine but not cimetidine (anti-H2). H-1 antagonists, 2-thiazolylethylamine and triazole produce dose response curves similar to histamine. The dose response curves of H-2 agonists betazole and dimeprit demonstrate an ED50 of greater than 10 to the minus 3rd power M. Further work is in progress to elucidate any possible interaction between histamine and its antagonists and cholecystokinin and cholinergic stimuli and to determine whether histamine participates in any physiologic responses of the pancreas to food ingestion.