Most post-mortem autoradiographic studies have described striatal dopamine D(2) receptor up-regulation due to chronic neuroleptic exposure. The aim of our study was to compare in-vivo striatal D(2) receptor density in neuroleptic-naive and neuroleptic-free schizophrenic patients. We included 28 young (mean age: 28+/-8 years) acute psychotic patients meeting DSM-IV criteria for schizophrenia or schizophreniform disorder. Enrolled patients were either first-episode neuroleptic-naive (n=12) or neuroleptic-free (n=16) after a minimum washout period of 7 days. All neuroleptic-free subjects had previously received neuroleptic treatment for a median period of 3.5 years. Both groups were evaluated using standard clinical scales. In-vivo striatal D(2) receptor binding was assessed by basal ganglia/frontal cortex ratios using (123)I-IBZM SPECT. No statistically significant differences were found in age or clinical assessment between neuroleptic-naive and neuroleptic-free schizophrenic patients. No differences were found in the basal ganglia/frontal cortex ratios of neuroleptic-naive (1.78+/-0.11) and neuroleptic-free (1.81+/-0.15) patients. No striatal uptake laterality was observed in either group. No correlation was demonstrated between BG/FC ratios and duration of illness, period of neuroleptic exposure or time of drug washout. We conclude that our neuroleptic-naive and neuroleptic-free schizophrenic patients did not show differences in striatal D(2) receptor binding, suggesting that IBZM-SPECT fails to detect D(2) receptor up-regulation induced by chronic exposure to neuroleptic drugs.