Reaction times are usually faster when stimulus and response occur at the same location than when they do not, even if stimulus location is irrelevant to the task (Simon effect). This effect was found with both horizontal and vertical stimulus-response arrangements. The same mechanisms have been proposed to be involved in either case. Here, we compared a horizontal and a vertical Simon task by means of a RT time-course analysis of the Simon effect. Also, we analysed the lateralised readiness potential (LRP), an index of covert response-preparation processes. In the horizontal task, the Simon effect decays over time and pre-activation occurs above the motor cortex ipsilateral to the stimulus. In contrast, the Simon effect does not decay over time and no early incorrect LRP deflection is observed in the vertical task. These findings suggest that typical activation accounts can fit only the horizontal Simon effect, while a translation explanation is more suitable for the vertical Simon effect.