Studies in animals and humans have demonstrated intrinsic activity in the brain during the resting state. The concept of the default-mode network (DMN) - a set of brain regions in which resting-state activity (RSA) activity is reduced in response to external stimuli - recently raised much controversy concerning the psychological correlates of RSA. However, it remains unclear how RSA interacts with stimulus-induced activity. Here we review studies in humans and animals that address how RSA interacts with stimulus-induced activity; we also discuss, conversely, how stimulus-induced activity can modulate RSA. Psychologically, the rest-stimulus interaction is relevant to predicting subsequent behavioral and mental states. We conclude that a better understanding of the rest-stimulus interaction is likely to be crucial to the elucidation of the brain's contribution to mental states.