Simon effects might partly reflect stimulus-triggered response activation. According to the response-discrimination hypothesis, however, stimulus-triggered response activation shows up in Simon effects only when stimulus locations match the top-down selected spatial codes used to discriminate between alternative responses. Five experiments support this hypothesis. In Experiment 1, spatial codes of each response differed by horizontal and vertical axis position, yet one axis discriminated between alternative responses, whereas the other did not. Simon effects resulted for targets on discriminating axes only. In Experiment 2, both spatial axes discriminated between responses, and targets on both axes produced Simon effects. In Experiment 3, Simon effects resulted for a spatial choice-reaction task but not for a go/no-go task. Even in the go/no-go task, a Simon effect was restored when a two-choice reaction task preceded the go/no-go task (Experiment 4) or when participants initiated trials with responses spatially discriminated from the go response (Experiment 5).