Near-infrared spectroscopy (NIRS) is a non-invasive optical technique which has been successfully used to register substantial cerebral ischemia. There are indications that NIRS is sensible enough to detect also small metabolic changes during the performance of cognitive tasks. In the present study, two-channel NIRS of left and right anterior frontal brain areas was applied to investigate brain oxygenation of 10 healthy subjects carrying out the continuous performance test (CPT). Significant differences between the left and right hemisphere were found. These consisted of different changes in deoxyhaemoglobin (HHB), but not in oxyhaemoglobin (O2HB) in right frontal brain areas compared to baseline during the test. Despite of some methodological restrictions, the findings suggest that the sensitivity of the NIRS-method is sufficient to detect brain oxygenation changes during cognitive activation. Furthermore, the results support the view that execution of the CPT is associated with prevalently right frontal activation.