Brain death protocols facilitate early recognition of death in patients on life support systems. When the clinical situation has deteriorated to a level where brain death is to be considered, it is essential that the effects of drugs be excluded. Most centrally acting drugs depress respiration and would be expected to affect apnoea testing of brain stem function. However, the pharmacodynamic and pharmacokinetic properties of drugs are altered when patients are critically ill, so projections made from data derived from less ill patients or normal volunteers are inappropriate. The entry of drugs into the brain is also altered in some disease states, but there are few data relating to the effects of central depressant drugs in the situation of a disrupted blood-brain barrier or brain damage. Drug screens can assist in determining whether drugs are present, but correct interpretation of the results depends on close liaison between the clinical and laboratory staff. It is in the patient's interests to avoid termination of life support if any centrally active drug is present, unless there are other categorical factors consistent with irreversible brain death, such as demonstrated lack of cerebral blood flow.