It can be extremely difficult to interpret the results of experiments in which a treatment is found to antagonize the behavioural effects of a drug. This article discusses strategies that can be used to help identify the nature of the antagonism and examines what such experiments tell us about the mechanisms underlying the drug's behavioural effects. Examples are taken from research with both benzodiazepines and ethanol. It is suggested that behavioural studies using different strategies to reduce the effects of a drug will further enhance our understanding of the mechanisms mediating the drug's effects. Such studies will include comparisons between the effects of chronic drug exposure (tolerance studies), genetic manipulations, and pharmacological treatments.