Background: Schizophrenia patients exhibit impairment in prepulse inhibition (PPI) of the acoustic startle response (ASR), suggesting a sensorimotor gating deficit. The serotonin-2A receptor (5-HT2AR) has been implicated in both the pathogenesis of schizophrenia and the PPI deficits of schizophrenia patients. Moreover, both schizophrenia and PPI are thought to be inheritable. We investigated the impact of three 5-HT2AR polymorphisms (A-1438G, T102C, H452Y) on PPI in schizophrenia patients.Methods: We analyzed the 5-HT2AR A-1438G, T102C, and H452Y polymorphisms and assessed startle reactivity, habituation, and PPI of ASR in 68 Caucasian schizophrenia inpatients. Patients were also examined with the Positive and Negative Syndrome Scale.Results: The 5-HT(2A)RA-1438G and T102C polymorphisms were incomplete linkage disequilibrium. Patients carrying the T102C TT and the A-1438G AA allele show significantly higher PPI levels and a faster early habituation compared with all other variants. 5-HT2AR A-1438G and T102C genotype explained approximately 11% of the PPI and early habituation variance. In contrast, the 5-HT2AR H452Y polymorphism did not affect startle parameters.Conclusions: Our findings suggest that PPI and h a bituation are modulated by 5-HT(2A)RA-1438G and T102C genotype in schizophrenia. Consequently, alterations within brain 5-HT2ARs may contribute to the PPI deficits in schizophrenia.