The effects of cystamine on gastric secretion were studied in conscious and anaesthetized rat preparations. In the conscious gastric fistula rat cystamine inhibited the basal acid output but increased pepsin output. This pepsinogogue action was inhibited by both atropine and metiamide. In the anaesthetized rat cystamine stimulated gastric acid output, an effect blocked by cimetidine which had an inhibitory E.D. 50 which was not significantly different from that obtained against histamine-stimulated secretion in this preparation. Atropine at high doses failed to inhibit the response. Depletion of mast cell histamine by compound 48/80 the secretory response to cystamine. In the light of these results possible mechanisms of action for the secretagogue effects of cystamine are discussed.