Methylphenidate (MPH) is a catecholamine transporter blocker, with dopamine agonistic effects in the basal ganglia. Response inhibition, error detection, and its mediating frontostriatal brain activation are improved by MPH in patients with attention-deficit/hyperactivity disorder. However, little is known about the effects of MPH on response inhibition and error processing or its underlying brain function in healthy individuals. Therefore, this study employed functional magnetic resonance imaging (fMRI) and 2 response inhibition tasks in 52 healthy males. Subjects underwent fMRI during a go/no-go task and a tracking stop-signal task after administration of 40 mg MPH and placebo in a double-blind, placebo-controlled, repeated-measures design. Results revealed task- and condition-specific neural effects of MPH: it increased activation in the putamen only during inhibition errors but not during successful inhibition and only in the go/no-go task. We speculate that task specificity of the effect might be due to differences in the degree of error saliency in the 2 task designs, whereas errors were few in the go/no-go task and thus had high saliency and the stop-signal task was designed to elicit 50% of errors in all subjects, diminishing the error saliency effect. The findings suggest that neural MPH effects interact with the saliency of the behavior under investigation.