Separate working memory domains for spatial location, and for objects, faces, and patterns, have been identified in the prefrontal cortex (PFC) of nonhuman primates. We have used functional magnetic resonance imaging to examine whether spatial and nonspatial visual working memory processes are similarly dissociable in human PFC. Subjects performed tasks which required them to remember either the location or shape of successive visual stimuli. We found that the mnemonic component of the working memory tasks affected the hemispheric pattern of PFC activation. The spatial (LOCATION) working memory task preferentially activated the middle frontal gyrus (MFG) in the right hemisphere, while the nonspatial (SHAPE) working memory task activated the NIFG in both hemispheres. Furthermore, the area of activation in the left hemisphere extended into the inferior frontal gyrus for the nonspatial SHAPE task. A perceptual target (DOT) detection task also activated the MFG bilaterally, but at a level approximately half that of the working memory tasks. The activation in the MFG occurred within 3–6 s of task onset and declined following task offset. Time-course analysis revealed a different pattern for the cingulate gyrus, in which activation occurred upon task completion. Cingulate activation was greatest following the SHAPE task and was greater in the left hemisphere. The present results support the prominent role of the PFC and, specifically, the MFG in working memory, and indicate that the mnemonic content of the task affects the relative weighting of hemispheric activation.