Repeated administration of amphetamine (AMPH) to rats results in an augmentation of the drug-induced locomotion and stereotypy. The studies reported below were directed at examining the potential role for some dispositional and peripheral sympathomimetic factors in mediating the enhanced stereotypy response. These included three factors associated with repeated AMPH administration: (1) the possible accumulation of AMPH in a peripheral mobilizable pool; (2) repeated sympathetic activation; and (3) AMPH metabolite-induced depletion of peripheral stores of norepinephrine. The approach utilized was to selectively reduce or mimic the peripheral actions of AMPH through the use of non-pharmacological or pharmacological manipulations which are relatively lacking in AMPH-like central stimulant effects. The results indicate that these factors cannot account for the augmentation of the behavioral response to AMPH and suggest that these behavioral alterations reflect changes in the responsiveness of brain mechanisms which mediate the behavioral effects of the drug.