Behavioral effects of the same dose of the same drug can vary in degree and direction between and within individuals. The present study examines behavioral base rates, feeding status, and dispositional differences as sources of inter- and intra-individual heterogeneity in drug response. Modulation of the effects of methylphenidate (MPD) on wheel running and acoustic startle by food deprivation was examined in three experiments. Freely fed or food deprived Harlan Sprague-Dawley rats (running study) or rats selectively bred for low (LoS) and high (HiS) saccharin intake (running and startle studies) were given MPD (10 mg/kg) or saline before testing. Overall drug effects and predictors of drug response were assessed. MPD increased running and startle amplitude and disrupted prepulse inhibition; systematic variation among rats of these effects and their modulation by food deprivation was observed. Deprivation-induced running predicted MPD's effect in Harlan SD and LoS rats. Observation of this relationship among commercial rats suggests that acute deprivation sensitivity has utility as a noninvasive marker for drug responses. Its observation in rats selected on a taste phenotype with known correlates points to fruitful avenues of research on stimulant drugs' mechanisms, especially in dopaminergic pathways, and may be relevant to their clinical usage.