The effects of clonidine on gastric acid secretion were studied in conscious dogs with both gastric fistulae and Heidenhain pouches. Clonidine infused systemically at graded doses under basal conditions produced a significant increase in acid secretion from both gastric fistulae and Heidenhain pouches. Acid secretion from gastric fistulae submaximally stimulated by pentagastrin was dose-dependently reduced by clonidine while 2-deoxy-D-glucose-induced secretion was completely suppressed. Under these conditions a significant enhancement of secretion from Heidenhain pouches was recorded. An increase in acid secretion from both main stomachs and Heidenhain pouches was observed for clonidine with submaximal doses of bethanechol and histamine as stimulants, though clonidine showed no effect on maximal stimulation by histamine. The stimulant effect of clonidine from gastric fistulae and Heidenhain pouches under basal conditions was fully prevented by cimetidine, while the inhibitory effect of clonidine on acid secretion stimulated by pentagastrin from gastric fistulae was reversed by yohimbine. The present results suggest that clonidine displays two simultaneous yet opposite effects on dog gastric secretion. The inhibitory effect might be mediated through a decrease of vagally released acetylcholine following the activation of alpha 2-adrenoceptors both at central and peripheral sites, while the stimulatory effect probably depends on the histamine-like properties of the drug.