We have examined whether propofol activates complement. In the first study, blood was mixed with saline, propofol or the lipid solvent for propofol, and the activated complement 3 (C3a) and 4 (C4a) concentrations in the supernatant were assayed. In the second study, blood and propofol were mixed with various levels of nafamostat mesilate (anti-complement agent) up to 0.3 mmol/l and the C3a was assayed. In the third study, the time course of plasma C3a concentration in patients during propofol anaesthesia was examined. The results showed that the lipid solvent activated complement and produced similar levels of C3a to propofol, probably via both the classical and alternative pathways. This activation was not inhibited by any of the nafamostat concentrations used. There was no significant change in plasma C3a concentration during propofol anaesthesia. These results suggest that C3a is generated by the lipid solvent, but its accumulation during propofol anaesthesia is minimal.