Although the kinetic profile of antipsychotics at dopamine D 2 receptor sites has been suggested to be important for antipsychotic action and dosing schedule, the kinetic profiles of the respective antipsychotic drugs in the brain have not yet been clearly defined. We aimed to estimate the time course of dopamine D 2 receptor occupancy from plasma pharmacokinetics and the apparent in vivo affinity parameter (ED 50; concentration to induce 50% occupancy). Dopamine D 2 receptor occupancies and plasma concentrations of risperidone, one of the atypical antipsychotics, were measured in five patients with schizophrenia using positron emission tomography (PET) with [ 11C]FLB 457. Measured dopamine D 2 occupancies were compared with those estimated from plasma kinetics and in vivo ED 50. Mean half-life of dopamine D 2 receptor occupancy of risperidone was about 80 h, while that of the plasma concentration was about 18 h. Dopamine D 2 receptor occupancy estimated from plasma pharmacokinetics and in vivo ED 50 was within 1 S.D. of the mean measured occupancy. Using plasma pharmacokinetics and in vivo ED 50, the time course of receptor occupancy could be calculated. The investigation of drug kinetics at receptors using PET would provide useful information for the evaluation of antipsychotics.