A comparison of the behavioral pharmacology of DOM and amphetamine in rats indicated that lower doses (0.10-1.0 mg/kg) of the two agents had similar effects on schedule-controlled food-reinforced and shock-avoidance behavior. Similarities were also noted in their effects on horizontally directed motor activity when testing was preceeded by a period of acclimation. However, most doses of DOM tended to decrease unacclimated motor activity, while amphetamine increased this behavior. Neuropharmacological antagonism studies indicated that brain catecholamines (CA) and serotonin (5-HT) are involved in the behavioral effects of both DOM and amphetamine. Cinanserin, a 5-HT receptor blocker, attenuated the behavioral disruptive effects of both agents on food-reinforced responding. Cinanserin attenuated the effects of all doses of DOM and those of higher doses of amphetamine on shock avoidance. When given prior to lower doses of amphetamine, there was a greater behavioral stimulation than when amphetamine was given alone. Prior depletion of brain CA with alpha-methyltyrosine (alpha-MT) did not affect DOM induced disruption of food-reinforced responding, while alpha-MT attenuated the behavioral effects of all doses of DOM and amphetamine on shock avoidance. These data suggest that DOM and amphetamine share a similar component in their mechanism of action which depends on the availability of a releasable pool of brain CA.