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Well-formed visual hallucinations (VH) are common in patients with Parkinson's disease (PD). The pathophysiology of VH in PD is unknown but may involve structures mediating visual processing such as the inferior temporal cortex. Serotonergic type 2A (5-HT(2A)) receptors have been linked to many psychiatric disorders, including psychosis. We hypothesized that enhanced 5-HT(2A) receptor levels may be involved in VH in PD. Autoradiographic binding using [(3)H]-ketanserin and spiperone, to define 5-HT(2A) receptors, was performed in 6 PD patients with VH, 6 PD patients without VH, and 5 healthy, age-matched controls. The cerebral regions studied included the orbitofrontal cortex, inferolateral temporal cortex, motor cortex, striatum, and substantia nigra. There was a significant (45.6%) increase in the levels of [(3)H]-ketanserin binding in the inferolateral temporal cortex of PD patients with VH when compared with PD patients without VH (54.3 +/- 5.2 fmol/mg vs. 37.3 +/- 4.3 fmol/mg, P = 0.039). Additionally, there was a significant increase in the levels of 5-HT(2A) receptors in the motor cortex of all PD patients taken as a group when compared with controls (57.8 +/- 5.7 fmol/mg vs. 41.2 +/- 2.6 fmol/mg, P = 0.0297). These results suggest that enhanced 5-HT(2A)-mediated neurotransmission in the inferolateral temporal cortex, a critical structure in visual processing, might be associated with the development of VH in PD. Our results provide new insights into the pathophysiology of VH in PD and provide an anatomical basis to explain why compounds with 5-HT(2A) antagonist activity are effective at alleviating this debilitating complication., ((c) 2010 Movement Disorder Society.)