By means of extracellular recordings, individual norepinephrine-containing neurons in the locus coeruleus of unanesthetized behaviorally responsive rats and squirrel monkeys were found to respond to specific sensory and behavioral conditions. In rats, distinct clusters of action potentials followed the presentation of various nonnoxious auditory, visual, or somatosensory stimuli at latencies of 15-60 msec. Increased discharge rates were also seen during periods of spontaneous electroencephalogram arousal in both species. In monkeys, these cells responded most vigorously to complex arousing stimuli such as a preferred food. Because the noradrenergic innervation of most forebrain regions arises from the locus coeruleus, these results allow prediction of situations under which this massive projection system would be active and suggest a physiological role for this chemically identified network in specific behavioral processes.