The cytochrome enzyme p4503A4 (CYP3A4) is thought to play a major part in the human metabolism of clozapine. Nefazodone is a potent and specific in-vivo inhibitor of CYP3A4. We co-administered nefazodone and clozapine in six patients and found that mean clozapine levels rose by 4% of baseline and norclozapine levels by 16%. Based on these observations, it is inferred that inhibition of CYP3A4 in vivo has minimal effects on clozapine metabolism. Nefazodone appears to be safe when co-administered,vith clozapine. Int Clin Psychopharmacol 14-185-187 (C) 1999 Lippincott Williams & Wilkins.