The process of memory encoding and consolidation occurs over time. Although the neural events specific to this time period are not fully known, it is well documented that learning can be disrupted during the process. The motor learning task F1, using positron emission tomography (PET) [15O]H2O functional imaging, consists of moving a robotic arm in a specified external force field (field A or field B) from a resting place to a target location. The external force field applied to the robotic arm and negotiated by the volunteer depends on the subject’s hand motion and requires learning for smooth execution. To determine the time course for this task’s motor memory formation, an interference paradigm was used. Earlier work had shown that a time-dependent pattern of memory consolidation for the task occurs during the 5–6 hours after initial presentation and practice in field A. After learning field A, the ability of a volunteer to learn another task (field B) progressively improves with time. To define the neural localization of this learning and consolidation, an imaging experiment was performed in which volunteers learned field B at variable times after learning field A: one group did so after 10 minutes, and another group, after 5.5 hours. Regional cerebral blood flow (rCBF) was assessed in each set of conditions. During the initial learning of field A in each of the conditions, the primary motor cortex and the prefrontal cortex were the regions significantly activated above control levels. These two regions showed the greatest activation early in the learning session and demonstrated a gradual reduction in activation after 40 minutes of training in field A. If a second task, field B, is presented 10 minutes after full training in field A, field B is learned poorly; presumably the motor memory consolidation process for A interferes with B. If the second task, field B, is presented at 5.5 hours after learning the first task, field A, that learning proceeds normally. Regions in the ventral prefrontal cortex appear to be involved in mediating the interference effect: the right and left ventral prefrontal cortex are highly active when the learning of field B interferes with the learning of field A. At 5.5 hours after learning A, the learning of field B does not interfere with A, nor does it activate the ventral prefrontal regions. These studies emphasize the time-dependent changes that occur in the brain after initial skill acquisition and suggest that motor memory consolidation and interference involve different regions of the brain.