The effects of human immunodeficiency virus (HIV) infection on central nervous system function were studied with the P3a and P3b event-related brain potentials (ERPs) in patients with HIV compared to unaffected matched controls (n = 14/group). All patients were on anti-viral medication for at least 2 months before testing. Auditory stimuli were employed in an easy 2-stimulus oddball discrimination task to obtain a typical P3b (P300) subcomponent. A 3-stimulus distractor paradigm also was employed in which the target/standard discrimination was very difficult, and an infrequent high-pitched tone non-target was presented to elicit the P3a subcomponent. Subjects responded only to the target stimulus in each task. P3a amplitude was significantly smaller for HIV compared to control subjects. No reliable P3b effects were obtained. The findings suggest that P3a rather than P3b may be a more sensitive measure of cognitive impairment in HIV patients on anti-viral medication.