Lateral presentation of relevant information facilitates manual responses if the side of relevant information corresponds to the side of the response. Recently, temporally overlapping EEG asymmetries over the central motor cortex and posterior sites were reported as a possible correlate of the sensory-motor integration of spatial information. The present study investigated whether sensory-motor integration of spatial information can occur with symbolic spatial information the same way as with laterally presented stimuli. The task required participants to respond to arrows (target stimuli), which were “flanked” (from above and below) by neutral stimuli or by other arrows (compatible or not). In Experiment 1, this task was compared to the same task with letters as stimuli and to an incompatible task where participants had to respond “against” the arrow direction. The effect of the flankers on response times was largest if subjects had to respond to the arrows in the common way. This was also the only task of Experiment 1 for which marked EEG asymmetries related to the direction of the flankers were observed. In Experiment 2, the onsets of target stimulus and flankers differed in time. Event-related lateralizations of the EEG over sensory and primary motor areas—as a lateralized readiness potential—were always, apparently automatically, evoked by flanking arrows, indicating automatic response activation evoked by symbolic spatial information. In accordance to recent theories of temporally decaying response activation, manual responses were affected only if the target was either shortly preceded by or appeared simultaneously with the flankers. The temporal overlap of EEG asymmetries related to direction encoding, automatic response activation, and to response preparation indicated that a widespread cortical network is activated by any salient directional information that enables subjects to respond quickly if the directional code of the stimulus overlaps with the directional code of the response.