The lectin pathway is a novel pathway for activation of the complement cascade, which is initiated by the binding of mannose-binding protein (MBP) to its carbohydrate ligands. We investigated whether the complement system was activated in vitro by glioma cells through this pathway to the C3 level. MBP was found to bind to all six glioma cell lines tested by using flow cytometric analysis. Binding of a complex of MBP-associated serine protease and MBP was observed in two of the cell lines examined, thereby resulting in C4 consumption. Activation of C3 was hemolytically evaluated in these two lines. C3 consumption was also observed in one. Based on these results, it is likely that recognition by MBP followed by complement activation occurs in certain glioma cell lines.