Although previous studies have shown that the human attention system is partially affected by chlorpheniramine, the effects of chlorpheniramine on human auditory selective attention have not yet been explored. This study examines the effects of a single dose of 4 mg ofdextro-chlorpheniramine on human auditory selective attention by means of the evaluation of the event-related brain potential (ERP) processing negativity (PN). The study sample consisted of 20 healthy male humans, who received either a single 4-mg dose ofdextro-chlorpheniramine or a placebo in a double-blind design. The subjects were given a dichotic listening task, in which they were instructed to press a response button upon detecting deviant tones (target) while their ERPs were recorded. In parallel, subjective tests evaluated the daytime sleepiness, overall vigor, and affect of the subjects. Results showed that the auditory selective attention is impaired under the effects of chlorpheniramine, as reflected by an attenuation of PN amplitude and by a decrease of performance in the group of subjects who took a single 4-mg dose ofdextro-chlorpheniramine. No subjective change in the daytime sleepiness, overall vigor, or affect of the subjects was observed. This lack of conscious awareness of the side effects may lead to situations of risk in tasks for which auditory information is important, because no subjective indicators of attention impairment are available to the subjects.