To examine the variations in regional cerebral blood flow during execution and learning of reaching movements, we employed a family of kinematically and dynamically controlled motor tasks in which cognitive, mnemonic and executive features of performance were differentiated and characterized quantitatively. During 15O-labeled water positron emission tomography (PET) scans, twelve right-handed subjects moved their dominant hand on a digitizing tablet from a central location to equidistant targets displayed with a cursor on a computer screen in synchrony with a tone. In the preceding week, all subjects practiced three motor tasks: 1) movements to a predictable sequence of targets; 2) learning of new visuomotor transformations in which screen cursor motion was rotated by 30 degrees -60 degrees; 3) learning new target sequences by trial and error, by using previously acquired routines in a task placing heavy load on spatial working memory. The control condition was observing screen and audio displays. Subtraction images were analyzed with Statistical Parametric Mapping to identify significant brain activation foci. Execution of predictable sequences was characterized by a modest decrease in movement time and spatial error. The underlying pattern of activation involved primary motor and sensory areas, cerebellum, basal ganglia. Adaptation to a rotated reference frame, a form of procedural learning, was associated with decrease in the imposed directional bias. This task was associated with activation in the right posterior parietal cortex. New sequences were learned explicitly. Significant activation was found in dorsolateral prefrontal and anterior cingulate cortices. In this study, we have introduced a series of flexible motor tasks with similar kinematic characteristics and different spatial attributes. These tasks can be used to assess specific aspects of motor learning with imaging in health and disease.