Cysteamine is a potent duodenal ulcerogen in rats. It has been demonstrated to inhibit gastric empyting, whose role in ulcer formation is unknown. In the present study the effect of cysteamine on gastric motility and emptying rate in rats was studied by direct fluoroscopic observation. The delayed gastric empyting was due to a pronounced relaxation of the stomach and a complete blocking of gastric peristalsis. These effects have their maximum within the first 4 h after administration of cysteamine. Thereafter peristalsis and gastric empyting slowly return. In controls contrast medium administered intragastrically was completely discharged from the stomach within 30 min. After cysteamine the first small amounts of contrast medium were discharged into the duodenum after 4 h, and contrast medium remained in the stomach for at least 12 h after administration. The size of the stomach reached a maximum after 3 h and approached normal values again after 12 h. Because of complete gastric retention the acid gastric secretions provoked by cysteamine probably accumulate in the stomach during the first 4 h after cysteamine administration, and because of the absence of peristalsis they are not mixed with gastric contents. After 4 h this pool of undiluted gastric secretions gradually is emptied into the duodenum, where the mucosal resistance is reduced by inhibition of the secretory activity of Brunner's glands, and ulceration rapidly develops. The time relationship is supported by histopathologic findings and measurements of gastric acid secretions after cysteamine. Vagotomy augmented the inhibitory effect of cysteamine on gastric motility. The relaxation was even more pronounced, and contrast medium was not discharged from the stomach within 24 h. In these rats cysteamine induced ulcerations in the stomach.