Primary motor cortex (MC) has been strongly implicated in motor processing, but there have been relatively few attempts to determine whether MC may also play a role in either sensory or context-dependent processing. In the present study, neuronal activity in MC was characterized in relation to the planning and execution of visually instructed limb movements whose trajectories were dissociated from their spatial targets. This design permitted the dissociation of neuronal activity related to motor processing from activity related to sensory or context-dependent processing. Two macaque monkeys were trained to perform a visually instructed, delayed reaching paradigm with indirect visual feedback. Subjects used the right forelimb to capture targets presented on a video display by moving a two-dimensional joystick whose position was reflected by a cursor. The target to be capture on each trial was indicated by a visual instruction stimulus (IS), which was separated from a movement-triggering stimulus (TS) by a variable delay. The direction of forelimb movement was dissociated from the location of the target by varying the spatial mappings between joystick and cursor across two conditions, unrotated (0 degrees offset between cursor and limb direction) and rotated (90 degrees offset). Task-related activity was recorded from a total of 180 MC neurons. The focus of this study was on directionally tuned neuronal activity that included phasic, stimulus-related activity following the IS; tonic, set-related activity between IS and TS; and phasic, movement-related activity following the TS. Of the entire sample of MC neurons with directionally tuned activity, 119 cells were tested both under rotation conditions, permitting dissociation of directional responses that depended on target locations from those that depended on limb trajectory. Task-related neuronal activity was classified as target dependent if it covaried exclusively with target location across both conditions, and as limb dependent if it covaried exclusively with limb trajectory. Directional activity that did not fulfill criteria for either target or limb dependence, because of changes across rotation conditions, was classified as complex. Approximately one quarter of MC neurons showed weak, but consistent, stimulus-related activity that was directionally tuned (24%, 29 of 119). Nearly all of the directionally classifiable stimulus-related activity was target dependent (94%, 15 of 16 responses), with the exception of a single limb-dependent response (6%, 1 of 16). A majority of MC neurons showed set-related activity that was directionally tuned (61%, 72 of 119). Of the directionally classifiable set-related activity, there were comparable numbers of target-dependent (37%, 16 of 43) and limb-dependent responses (35%, 15 of 43), with the remainder being complex (27%, 12 of 43). Movement-related activity following the TS was considered to be early or late, depending on whether it preceded or followed the onset of movement. The large majority of MC neurons showed early movement-related activity that was directionally tuned (86%, 102 of 119): among those whose neurons early activity was directionally classifiable, there were only one third as many target-dependent responses (14%, 11 of 79) as limb-dependent responses (43%, 34 of 79), with the remainder being complex (43%, 34 of 79). There was also a large majority of MC neurons that showed late movement-related activity that was directionally tuned (84%, 100 of 119): among those whose late activity was directionally classifiable, there were only one ninth as many target-dependent responses (5%, 4 of 88) as there were limb-dependent responses (41%, 36 of 88), with the remainder being complex (55%, 48 of 88). The instructed delay task employed in this study required a sensory-to-motor transformation through which the instructed target location was associated with a limb movement of the appropriate direction. (ABSTRACT TRUNCATED)