The striatal D2 receptor density/affinity index was assessed using positron emission tomography and 76Br-Bromolisuride in 15 schizophrenics, first untreated, and afterwards receiving neuroleptics, and in 14 control subjects. The patients received low or conventional doses of neuroleptics. The schizophrenics receiving low doses (n = 6) had preponderant negative symptoms. Mean D2 receptor occupancy was 24 ± 20%. Despite this weak central D2 receptor blockade, a significant decrease in negative symptoms was observed, a result consistent with the hypothesis of a disinhibitory action of some neuroleptics administered in low doses. The patients treated with conventional doses (n = 9) had mixed positive and negative symptoms, and the mean D2 receptor occupancy was 54 ± 13%. Significant decreases in positive symptoms, but also in negative symptoms, were obtained with this treatment. Before treatment, there was no significant difference in the striatal D2 receptor density/affinity index between: 1) patients and controls, 2) negative and mixed schizophrenics, and 3) the subsequent responder and non-responder patients. In addition, the D2 dopamine receptor occupancy by neuroleptics did not significantly differ in responder or nonresponder patients, suggesting that the central D2 dopamine receptor blockade is a necessary, but insufficient condition to account for the antipsychotic effect of neuroleptics.