These experiments were designed to test the hypothesis that novel auditory stimuli lead to phasic and/or tonic increases in locus coeruleus (LC) cell firing, which may be a necessary condition for the occurrence of P300 potentials. Event-related potentials (ERPs) and LC unit activity were simultaneously recorded from three awake macaque monkeys exposed to an auditory "oddball" paradigm. Oddball stimuli resulted in probability-sensitive potentials resembling the human P3a component. Twenty-five percent (3/12) of LC units showed small phasic enhancements of LC firing after infrequent but not frequent tones. A comparison between histograms elicited by the two types of stimuli revealed significant effects of stimulus sequence. This pattern suggested a slight activation by rare tones, followed by a brief inhibition of firing in the subsequent trial. These data suggest that changes in LC activity during oddball paradigms are subtle, heterogeneous, and influenced by the subject's level of arousal and vigilance.