Acute exposure to methylphenidate (0.0, 5.0, 10.0, or 20.0 mg/kg) or amphetamine (0.0, 0.5, 1.0, 2.0, or 4.0 mg/kg) dose-dependently increased horizontal activity. The amphetamine-induced increase in activity was progressively augmented with repeated exposures over 7 days. In contrast, methylphenidate (20.0 mg/kg)-induced increases in activity became smaller with repeated exposures. Subthreshold doses of methylphenidate (1.0 or 5.0 mg/kg) were ineffective in stimulating motor activity even after 7 daily exposures. These findings suggest that, although sensitization develops with chronic amphetamine treatment, the consequence of chronic exposure to methylphenidate is tolerance. These data are discussed in terms of the different mechanisms through which methylphenidate and amphetamine affect central dopamine release.