Near-infrared spectroscopy (NIRS) allows noninvasive, in vivo measurement of changes in the concentrations of oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) in brain tissue based on their distinctive optical properties. A previous NIRS investigation on healthy subjects (Fallgatter and Strik 1997) found indications of right frontal activation during a Continuous Performance Test (CPT) that are consistent with results from positron emission tomography (PET) and event-related potentials studies. The indications consisted of right frontal blood oxygenation changes, consistent with a hemodynamic response, along with a significant left frontal increase in HHb. The current study investigated whether this characteristic lateralized frontal NIRS activation pattern was present in a group of nine schizophrenia patients during the execution of a CPT. In contrast to the previous study, no overall or hemispheric activation effects were found in the schizophrenia subjects. Direct comparison of the results of the two studies confirmed group differences, with a lack of lateralized activation in schizophrenia patients. Furthermore, a trend of higher left/right HHb ratios at rest and during activation was found in patients with schizophrenia. The finding is interpreted as a sign of reduced specific lateralized frontal reactivity, possibly based on a left hemisphere functional deficit.