The effects of the duodenal ulcerogens cysteamine and propionitrile on gastroduodenal myoelectric activity and intraluminal pressure in the fasted rat as well as on contractility of isolated gut muscle strips were investigated. Duodenal ulcerogens, unlike the nonulcerogen but toxic analogue ethanolamine, caused an early disruption of the myoelectric migrating complex, a marked increase in the spiking activity, and a decrease in the frequency of the slow waves in the duodenum. Both the increased spiking activity and the decreased slow wave frequency were dose dependent for cysteamine. Manometrically recorded contractions at the stomach corpus, midantrum, and antropyloric region as well as in the proximal duodenum of the conscious rat showed decreased contractions at the corpus and midantrum and an increase at the pyloric and duodenal sites during an intravenous infusion of cysteamine. In vitro studies demonstrated that circularly or longitudinally cut muscle strips taken from different regions of the stomach and duodenum responded to cysteamine with increased contractility. In summary, the duodenal ulcerogens cysteamine and propionitrile rapidly induce motor abnormalities in the stomach and duodenum of the rat. In vitro studies suggest that a cholinergic mechanism may be involved. It is possible that motor changes play a role in the pathogenesis of the experimentally induced duodenal ulcers.