Practice of a novel task leads to improved performance. The brain mechanisms associated with practice-induced improvement in performance are largely unknown. To address this question we have examined the functional anatomy of the human brain with positron emission tomography (PET) during the naive and practiced performance of a simple verbal response selection task (saying an appropriate verb for a visually presented noun). As a control state, subjects were asked to repeat the visually presented nouns. Areas of the brain most active during naive performance (anterior cingulate, left prefrontal and left posterior temporal cortices, and the right cerebellar hemisphere), compared to repeating the visually presented nouns, were all significantly less active during practiced performance. These changes were accompanied by changes in the opposite direction in sylvian-insular cortex bilaterally and left medial extrastriate cortex. In effect, brief practice made the cortical circuitry used for verbal response selection indistinguishable from simple word repetition. Introduction of a novel list of words reversed the learning-related effects. These results indicate that two distinct circuits can be used for verbal response selection and normal subjects can change the brain circuits used during task performance following less than 15 min of practice. One critical factor in determining the circuitry used appears to be the degree to which a task is learned or automatic.