Risperidone (RIS) is a novel antipsychotic agent whose pharmacokinetics have yet to be fully determined. In particular, little is known about RIS following an overdose. We report the pharmacokinetics following ingestion of a high dose of RIS by serially measuring the plasma concentration in two patients. These patients were admitted in a comatose state following an intentional overdose of RIS; all patients survived. In the first patient, 14 mg of RIS had been ingested 2 hr before the first blood sample was obtained. The second patient ingested an estimated 90 mg of RIS. Seven time-points were determined. The maximum concentration of unaltered RIS was 325 ng/mL and that of the principal metabolite (9-hydroxy-risperidone: 9-OH RIS) was 139 ng/mL. By plotting the time-concentration curve for the active fraction (RIS plus 9-OH-RIS) in the first and second patients, the half-life of RIS following overdose was determined and was approximately 12.7 hr and 17.8 hr, respectively. These values are similar to the half-life of RIS in healthy individuals ingesting a therapeutic dose. Two patients did not developed parkinsonism nor dystonia, and were discharged without sequelae.