It is difficult to discriminate clinically the etiology of small pancreatic cysts using conventional methods. Endoscopic ultrasonography can delineate small lesions. In order to help differentiate the etiology of cystic lesions of the pancreas by endoscopic ultrasonography, we investigated morphological changes following stimulation of the pancreatic secretion with secretin. After an intravenous injection of secretin (50 CU), the size, shape, and echogenicity of a cyst smaller than 2 cm were recorded for 15 min. Of 17 cases examined, 10 patients showed an alteration of these factors. These cases were thought to be nonneoplastic cysts, which included all six cases where communication to the main pancreatic duct was demonstrated by ERCP. Five cases of neoplastic cyst did not show the change in shape and size. These results indicate that secretin stimulation provides useful information in the diagnosis of the etiology of pancreatic cyst by endoscopic ultrasonography.