It has been known for over 45 years that electrical stimulation of the midbrain reticular formation and of the thalamic intralaminar nuclei of the brain alerts animals. However, lesions of these sectors fail to impair arousal and vigilance in some cases, making the role of the ascending activating reticular system controversial. Here, a positron emission tomographic study showed activation of the midbrain reticular formation and of thalamic intralaminar nuclei when human participants went from a relaxed awake state to an attention-demanding reaction-time task. These results confirm the role of these areas of the brain and brainstem in arousal and vigilance.