Vigilance behavior, or watch keeping, involves the focusing of attention on the detection of subtle changes in the environment that occur over a long period of time. We investigated the time course of changes in brain activity during the continuous performance of a 60-min auditory vigilance task. The task required the detection of an intensity drop that occurred in 5% of the auditory stimuli. Six 1-min samples of cerebral blood flow (CBF) and electroencephalographic (EEG) activity were obtained at l0-min intervals during the vigilance performance. Changes in CBF were measured by means of positron emission tomography (PET). Performance data (hits, false alarms, reaction time) were analyzed across six 10-min blocks. Eight healthy male volunteers participated in the study. During the 60-min test, the number of correct detections (hits) did not change, but both the reaction time and EEG activity in the theta (4 to 7 Hz) range progressively increased across testing. CBF in several subcortical structures (thalamus, substantia innominata, and putamen) and cortical areas (ventrolateral, dorsolateral, and orbital frontal cortex; parietal cortex; and temporal cortex) decreased as a function of time-on-task; changes in the cortical regions were limited to the right hemisphere. Blood flow also decreased in the temporalis muscles. At the same time, CBF increased in several visual cortical areas including the left and right fusiform gyri. Furthermore, the thalamic blood-flow response co-varied with that in the substantia innominata, the ponto-mesencephalic tegmentum, and the anterior cingulate cortex. The right ventrolateral-frontal blood-flow response covaried with that in the right parietal, orbitofrontal, and dorsolateral frontal cortex. 'Iko main conclusions are drawn from the obtained data. First, we suggest that the observed time-related changes in reaction time, EEG activity, and blood flow in the temporalis muscles are related to changes in the level of arousal (alertness) and that CBF changes in the thalamus-related neural circuitry represent a brain correlate of such changes. Second, we speculate that time-related CBF decreases in cortical regions of the right hemisphere underlie a shift from controlled to automatic attentional processing of the auditory stimuli.