The serotonin 5-HT(2A) receptor is suspected to be involved in a number of psychiatric disorders, including schizophrenia. In particular, atypical antipsychotics have antagonistic effects on the 5-HT(2A) receptors, supporting a specific role of the 5-HT(2A) receptor in the pathophysiology of this disease. The aim of this study is to investigate cortical and subcortical 5-HT(2A) binding in neuroleptic-naive schizophrenic patients. Fifteen neuroleptic-naive patients diagnosed with schizophrenia (age 27.5+/-4.5 years), 11 men and 4 women, and 15 healthy control subjects matched for age (28.5+/-5.7 years) and gender underwent a 40 min positron emission tomography (PET) study using the 5-HT(2A) antagonist, [(18)F]altanserin, as a radioligand. PET images were co-registered to 3 T magnetic resonance images (MRIs) for each individual subject, and ROIs were applied automatically onto the individual MRIs and PET images. The cerebellum was used as a reference region. The binding potential of specific tracer binding (BP(p)) was used as the outcome measure. No significant difference was seen in cortical receptor distribution between patients and controls. An increase in 5-HT(2A) receptor binding in the caudate nucleus was detected in the group of schizophrenic patients (0.7+/-0.1) when compared to the healthy controls (0.5+/-0.3) (p=0.02). Our results confirm other in vivo findings of no difference in cortical 5-HT(2A) receptor binding between first-episode antipsychotic-naive schizophrenic patients and age- and gender-matched healthy control subjects. However, a preliminary finding of increased 5-HT(2A) binding in the caudate nucleus requires further investigation to explore the relation of subcortical and cortical 5-HT(2A) receptor binding.