The purpose of cerebral autoregulation is to keep cerebral blood flow constant during variations of cerebral perfusion pressure (CPP). Recently, the autoregulatory response was reported to be greater during arterial blood pressure (ABP) increase than during decrease following repeated induced changes in ABP in 14 brain-injured subjects. The goal of this study was to further investigate the asymmetry of autoregulation during spontaneous increases and decreases of CPP in a larger group of brain injury patients. Data recordings (N=727) of CPP and cerebral blood flow velocity (CBFV) in 210 subjects with traumatic brain injury (TBI) were studied. Autoregulation was assessed using moving correlation indices (Mx) between CPP and CBFV. Periods of increasing and decreasing CPP were separately correlated to corresponding CBFV in order to assess autoregulatory responses to upward (upMx) and downward (downMx) changes of CPP. These correlation indices range from -1 to +1; negative or zero values indicate intact autoregulation, whereas positive values indicate impaired autoregulation. Only data with defined strong CPP variations were evaluated. Strong CPP variations were found in 84 recordings of 53 patients. On average (+/-SD) upMx was significantly lower than downMx (0.05+/-0.49 versus 0.14+/-0.54; p < 0.005). Despite this difference, upMx and downMx were strongly correlated with each other (R=0.82; p < 0.001). In conclusion, the autoregulatory response was significantly greater during increase than during decrease in CPP. The results may indicate non-linear behavior of cerebral autoregulation.