A method of operating an internal combustion engine with at least one piston-cylinder unit, and preferably a plurality of the piston-cylinder units, whereby, in a detection mode of the internal combustion engine one or more knock-promoting measures are taken until knocking has occurred in at least one piston-cylinder unit, and the measure(s) is/are intensified until a termination criterion is reached, whereby it is detected in which of the piston-cylinder units knocking has occurred, and whereby, in piston-cylinder units detected as knocking, the ignition time for a normal operating mode of the internal combustion engine is retarded.