summary Extra care must be taken in treating patients with clozapine because of the serious side-effects. A 44-year-old man with schizophrenia developed delirium on two occasions immediately after restarting clozapine at the dosage he had previously tolerated well; the clozapine-free periods had lasted 2 and 10 days respectively. Because of this 're-challenge' it seems very likely that there is a causal relation between the direct resumption of treatment with clozapine and delirium. Even if clozapine treatment is interrupted for only a short time it is important that the 'new' course begins with a low dosage and is increased very cautiously until it reaches the former, tolerated level.