The effects of cocaine withdrawal on the latency of the P300 cognitive event-related potential were studied in 36 subjects. All subjects had used cocaine within 48 h of admission to an inpatient unit. P300 was recorded in a traditional auditory oddball paradigm 2 and 6 days following admission. P300 latency decreased from day 2 to day 6 in subjects with a history of intravenous use, but was unchanged in subjects who had only used cocaine orally. The neurotransmitter systems mediating this effect, and the differential cognitive effects of route of administration are discussed.