In the present study, we examined whether or not novel stimuli affect performance in a focused attention task. Participants responded to a central target while an irrelevant distractor in the visual display was occasionally changed. In Experiment 1, both target and distractor were presented centrally within the focus of attention. In Experiment 2, a central target was presented along with an irrelevant distractor at a peripheral location, outside the focus of attention. Novel distractors were associated with longer latencies and enhanced orienting responses (as measured by skin conductance responses) only when presented at an attended location. In contrast, as is demonstrated in Experiment 3, the same peripheral novel distractors interfered with task performance when they possessed task-relevant information. These results indicate that there is a fundamental difference between novel stimuli and task-relevant stimuli. Whereas the former exert influence only within the focus of attention, the latter affect performance even when positioned in an unattended location. Our findings have important implications for the operation of visual attention.