Transcranial Doppler sonography (TCD) is a non-invasive method to assess cerebral blood flow velocity (CBFV) and hence cerebral blood flow during cognitive activation. Major cognitive dysfunctions have been consistently reported in patients with schizophrenia, and important deficits have been observed with respect to prefrontal functions. However, prefrontal activation in schizophrenics has not been investigated with TCD despite its potential to examine short-term changes of cerebral blood flow. The Wisconsin Card Sorting Test (WCST) and the Tower of Hanoi puzzle were administered to 11 right-handed schizophrenics and 20 healthy controls. The middle and anterior cerebral arteries were pairwise insonated. Schizophrenics showed decreased CBFV during the initial phase of both prefrontal functions and the steady-state phase of the Tower of Hanoi. In healthy controls, there was a succession of three significantly different phases of mean CBFV during the Tower of Hanoi, and there was no such modulation in schizophrenics. Immediately after category shift in the WCST, there was an increase of mean CBFV in healthy controls, but not in schizophrenics. In conclusion, transcranial Doppler sonography was able to detect differing specific alterations of CBFV during two prefrontal tasks in healthy controls and patients with schizophrenia. Importantly, the results of this study imply a degraded pattern of CBFV changes over time in schizophrenia during prefrontal activation.