The effects of the opiate antagonist naloxone on electrophysiological measures of human selective attention were examined utilizing a paradigm which dissociates selective information processing from any concurrent processes of general arousal that may be present. Subjects were injected with naloxone (2 mg, i.v.) or placebo prior to performing a three-channel selective listening task. The measure of selective attention was the difference between the auditory event-related potential (AERP) to a sequence of tones when they were attended and to the same sequence of tones when they were ignored. Typically, the AERP to attended channel tones is more negative, and this increased negativity is designated the attention effect. In this study, naloxone produced a significant augmentation of the AERP attention effect at frontal electrode sites, primarily by decreasing the negativity of AERPs to inattended tones. Naloxone had no effect on the AERPs from the undistracted and divided attention tasks or on the sensitivity of the AERP to a physical parameter of stimulus presentation, interstimulus interval. The effects of naloxone on selective attention appear to be independent of any alterations in arousal, as the drug had no effect on autonomic measures, reaction times, or auditory sensitivity, and the attention changes could be dissociated from any naloxone-induced alterations of mood. These data indicate that naloxone can have the specific effect of increasing AERP measures of selective information processing, thus suggesting a role for endogenous opioid peptides in the regulation of auditory selective attention in humans.