Inhibition of return (IOR) is a phenomenon that has been thought to be closely associated with attention mechanisms. In particular, it might arise from the operation of an attentional mechanism that facilitates visual search by inhibiting both covert attention and eye movements from returning to recently inspected locations. Although IOR has received a great deal of research interest, and mechanisms involving sensory, perceptual, and motor consequences have been proposed, no consensus has yet been reached regarding the stages of information processing at which IOR operates. In the present study, we utilized event-related potential (ERP) measures of visual and motor processes to investigate the processing changes underlying IOR. In three experiments, involving localization, detection, or Go-NoGo discrimination, participants were required to make manual responses to target stimuli. In each of these experiments, IOR was associated with a slowing of premotor processes as indicated by a modulation of the onset of the target-locked lateralized readiness potential (LRP). However, the duration of motor processes was not affected (response-locked LRP latency). Consistent with a perceptual locus of IOR, the amplitudes of the occipital ERP peaks were reduced for targets at cued locations relative to those at uncued locations. These and earlier results together provide considerable support for a model in which salience mechanisms that guide attention orienting are also affected by IOR, in that processing a stimulus at a location results in a lowering of its salience for future processing, making orienting to that location, and responding to targets presented there, more time consuming.