Clozapine, a new antipsychotic drug without extrapyramidal side effects and with strong sedating potency, can produce acute symptoms of central anticholinergic toxicity. The authors report that physostigmine, a reversible anticholinesterase agent, which can pass the blood-brain barrier, was effective in reversing the clozapine-induced brain syndrome in two patients. Physostigmine also reduced one patient's tachycardia.