Background: The mechanisms underlying cognitive deficits found in a number of patients with breast cancer treated with adjuvant chemotherapy are still unclear. In the current study, we used a combination of measures of brain electric activity and cognitive performance during information processing to elucidate the origin of these cognitive deficits. Patients and Methods: Twenty-nine patients at high risk with breast cancer treated with adjuvant conventional-dose cyclophosphamide/ epirubicin/5-fluorouracil or adjuvant high-dose cyclophosphamide/ thiotepa/carboplatin were compared with 23 patients with stage I breast cancer not treated with chemotherapy approximately 4 years after completion of treatment. We studied reaction times and the amplitudes and latencies of the P3, an electrophysiologic index of information processing, in a task with different conditions related to input, central, and output processing of information. Results: The amplitude of the P3 component was significantly reduced in patients with breast cancer treated with high-dose cyclophosphamide/ thiotepa/carboplatin compared with patients with breast cancer not treated with chemotherapy. We observed no significant differences in reaction times and P3 latency between the treatment groups. Conclusion: Our data show electrophysiologic alterations in patients with breast cancer treated with high-dose chemotherapy 4 years after completion of treatment. The observed P3 reduction might be a result of suboptimal phasic cortical arousal and problems with the allocation of processing resources in these patients.