The occupancy of the atypical neuroleptic quetiapine (Seroquel) at the D 2 dopamine receptor was investigated using the PET tracers 11Craclopride and N- 11Cmethylspiperone in a group of five schizophrenic patients. A steady-state treatment condition was ensured by dosing the patients with 750 mg quetiapine daily during 3 weeks followed by a period of tapering off the dose. For each patient, PET examinations were performed with both tracers at two of the following doses: 750, 450, 300 and/or 150 mg. As control, a group of six healthy untreated volunteers was investigated. The D 2 binding potential in the putamen and the caudate nucleus was determined by using an evaluation method based on the method proposed by Patlak and Blasberg. The receptor occupancy was determined by assuming that the group of healthy volunteers is representative of untreated drug-naive schizophrenic patients. While a significant linear trend of increasing occupancy with increasing quetiapine dose (reaching 51%±10% occupancy at the 750 mg dose) was detected with 11Craclopride ( P<0.01), no such trend was apparent for N- 11Cmethylspiperone ( P>0.09, maximal occupancy values were 2% ±3%, measured for the group of three patients on 450 mg). The study suggests that N- 11Cmethylspiperone cannot be used for the assessment of D 2 receptor occupancy induced by quetiapine. The result is discussed in terms of endogenous dopamine, tracer kinetics and equilibrium dissociation constants.