Four experiments examined the effects of d-amphetamine on lateralized direction preference, circling behavior, and perseveration. The nature as well as the magnitude of the behavioral response to amphetamine was dependent upon the testing situation. Whereas 5.0–10.0 mg/kg of the drug induced a robust circling behavior in a circular alleyway, it required 10.0 mg/kg of amphetamine produce a significant turn preference in an open field exploratory situation. In a symmetrical Y-maze, mice displayed spontaneous alternation behavior characterized by an exploratory pattern involving different arm sequences. After amphetamine administration, spontaneous alternation was reduced and pronounced perseverative patterns of exploration were evident at dose levels similar to those that induced rotational behavior. Directional preferences could not account for the exploratory patterns in the Y-maze of animals in the undrugged state, or under the influence of amphetamine regardless of dose. Since lateralized motor asymmetries after amphetamine were limited by the behavioral context in which the effects of the drug were evaluated, it was argued that rotational behavior cannot be considered to be a simple mechanistic behavior. Rather, in addition to the expression of a side preference, it involves a drug-induced perseverative tendency. On the basis of these data, it was suggested that evaluation of the direction of turning in an open field is a less biased measure of spatial preference following amphetamine administration. It was further argued that perseverative behavior is a prepotent response to amphetamine and the possibility of lateralized attentional asymmetries was discussed.