Drug-disposition studies of orally administered quinidine in four normal healthy volunteers indicated that phenobarbital and phenytoin reduced the half-life of quinidine by approximately 50 per cent (control, 3.0 to 6.1 hours, and with anticonvulsants, 1.6 to 2.6 hours). Alterations of similar magnitude in the apparent plasma clearance of quinidine after oral administration (control 20.0 to 32.0 liters per hour; with anticonvulsant 44.0 to 94.0 liters per hour) suggest that this effect is probably due to an increase in the rate of metabolism of quinidine, although decreased absorption cannot be entirely ruled out. In two index patients the concomitant use of anticonvulsant drugs resulted in inadequate blood levels of quinidine with standard dosages of that drug.