Phenytoin removal was followed in a patient undergoing plasmapheresis for thrombotic thrombocytopenic purpura. It was determined that 10% of total body phenytoin was removed with each two plasma volume exchanges, which is two to four times that reported with hemodialysis or peritoneal dialysis. During each 4- to 5-hr apheresis, serum phenytoin levels fell an average of 3.2 micrograms/ml and the phenytoin clearance by plasmapheresis was 21.9 +/- 2.1 ml/min (equal to the patient's endogenous clearance of 20.8 ml/min). Adjustment in drug doses were necessary such that, at steady state, the patient required 600 mg/day phenytoin to maintain therapeutic serum levels. These data indicate that plasmapheresis can clear the body of a significant amount of phenytoin and that increased doses may be required to maintain serum phenytoin levels. The potential use of apheresis in phenytoin overdose warrants further examination.