Diphenhydramine causes drowsiness and performance decrements in some tasks whereas terfenadine generally does not. This study examined central nervous system (CNS) differences in response to the administration of diphenhydramine (50 mg) and terfenadine (60 mg) up to 3 h after drug administration. Two evoked potential measures, the Brainstem Auditory Evoked Potential and the Pattern Reversal Evoked Potential (PREP), assessed CNS function. Other measures of CNS function, cognitive performance and subjective states administered included Critical Flicker Fusion, the Baddeley Grammatical Reasoning Test, Digit Symbol Substitution, the Profile of Mood States, and the Environmental Symptoms Questionnaire. Significant increases in PREP latencies (N $($$$) over bar 75, P $($$$) over bar 100 and N $($$$) over bar 145) occurred after orally ingesting diphenhydramine. No other significant drug effects were observed. The significant increase in the PREP latencies indicate diphenhydramine's presence in the cerebral cortex results in a slowing of visual information processing. The lack of significant findings for terfenadine is probably a result of its difficulty in penetrating the blood-brain barrier.