The correct use of ‘fold increase’ is analogous to the use of ‘percent increase’, which people interpret unambiguously. Say, for example, that a clinical drug–drug interaction study showed that a CYP3A4 inhibitor caused the area under the concentration-time curve (AUC) of a CYP3A4 substrate to increase from 500 to 1500 ng•h/ml. The larger number is 300% of the lower number, but it is only 200% higher. That is because we build the increase on top of the base of the lower number – we do not include it in the multiple. The increase is 1000 ng•h/ml, which is 200% of the 500 ng•h/ml base. Likewise with ‘times’; 1500 ng•h/ml is three-times 500 ng•h/ml, but it is only two-times higher. And likewise again with ‘fold’, the larger number is threefold the lower number, but it is only twofold higher. At least, it should be that way.