The value of physostigmine treatment of unconsciousness due to self-poisoning by tricyclic antidepressant drugs (TAD) was evaluated in 10 patients, and the following conclusions are drawn: 1. A slow i.v. injection of 2 mg of physostigmine produces a clear-cut increase in consciousness within 15 min if a TAD (or other drugs with central anticholingeric potencies) is mainly responsible for the poisoning. This "test dose" can give valuable diagnostic information. 2. Repeated i.v. injections seem of little practical value, since they may be expected to produce a state with rapid shifts in the level of consciousness. 3. If the test dose has a positive effect, immediate i.v. infusion of 4 mg physostigmine/h will maintain a high level of consciousness. Infusion should be stopped every sixth hour for about 30 min to check whether the level of consciousness still falls upon withdrawal of therapy 4. In cases of massive TAD overdosage, i.v. injection of physostigmine may increase the risk of grand mal seizures. 5. No signs of enhanced peripheral cholinergic activity following physostigmine are seen if 30 mg of propantheline is given i.v. every sixth hour. 6. No evidence has been produced that the morality rate in TAD poisoning is lower following physostigmine treatment whan with conventional supportive care. There must be the usual preparedness for cardiac complications.