The plasma concentration of N-desmethylmethsuximide in patients receiving chronic methsuximide therapy averages about 700 times the concentration of the parent drug. Both compounds were measured simultaneously by quadrupole mass fragmentography in the plasma of 17 patients receiving methsuximide for various types of epilepsy. Because methsuximide is only slightly more effective than N-desmethylmethsuximide in anticonvulsant tests on laboratory animals, it is likely that Ndesmethylmethsuximide is primarily responsible for seizure control in these patients. Although more study is needed to define the precise range of therapeutically effective plasma concentrations, plasma levels of N-desmethylmethsuximide below 10 mcg per milliliter appear to be ineffective while those above 40 mcg per milliliter are toxic.