Working memory (WM) is the ability to keep a limited amount of information "on line" for immediate use during short intervals. Verbal WM has been hypothesized to consist of neuroanatomically segregated components, i.e., maintenance (storage, rehearsal, and matching) and manipulation (reordering or updating), corresponding to ventrolateral and dorsolateral prefrontal cortex. Previous imaging studies of maintenance vs manipulation processes in WM have produced inconsistent results, which may have been due to methodological issues such as low statistical power and the use of insertion (subtraction) designs. In the present functional magnetic resonance imaging study we used parametric versions of both a prototypical maintenance task (Sternberg) and a prototypical manipulation task (n-letter back task) in 21 healthy subjects. Increased signal correlated with load common for both tasks was found in bilateral dorsolateral and anterior prefrontal, left ventrolateral prefrontal, and bilateral parietal regions. Workload x task interactions were found in bilateral dorsolateral prefrontal cortex for manipulation vs maintenance, but also for responding vs encoding (storage) in the maintenance task. Therefore, our data support a functional rather than a neuroanatomical distinction between maintenance and manipulation, given our finding that these tasks differentially activate virtually identical systems.