Previous studies have demonstrated the ability of the [11C]raclopride positron emission tomography (PET) technique to measure behaviorally induced changes in endogenous dopamine transmission in humans. However, these studies have lacked well matched sensorimotor control conditions, making it difficult to know what sensory, cognitive, or motor features contributed to changes in dopaminergic activity. Here we report on [11C]raclopride PET studies in which healthy humans performed card selection tasks for monetary rewards. During separate scans, subjects completed a variable ratio (VR) reward schedule with a 25% reward rate in which they did not know the outcome of their responses in advance, a fixed ratio (FR) 25% reward schedule in which outcomes were fully predictable, and a sensorimotor control (SC) condition involving similar sensory and motor demands but no rewards. Relative to the SC condition, the FR schedule produced only modest increases in dopamine transmission and no decreases relative to the SC condition. In contrast, the VR schedule produced significant increases in dopamine transmission in the left medial caudate nucleus while simultaneously producing significant decreases in other areas of the caudate and putamen. These data indicate: (1) the feasibility of measuring alterations in dopamine transmission even after controlling for sensorimotor features and (2) the complex and regionally specific influence of VR schedules on dopamine transmission. The implications of these results are discussed in relation to conflicting models of dopaminergic functioning arising from studies using electrophysiological and microdialysis techniques in animals.