Background: Serotonergic system abnormalities have been implicated in the pathogenesis of schizophrenia. The 5-HT2A receptor gene polymorphism has long been implicated to play a role in the pathogenesis of schizophrenia. Aim: In this study, we assessed the relationship of schizophrenia and its subgroups with 5-HT2A receptor gene polymorphism, and attempted to evaluate a possible correlation between the severity and prognosis of the illness and 5-HT2A receptor gene polymorphism. Method: Our study comprised 141 unrelated subjects who strictly met DSM-IV criteria for schizophrenia, and 79 healthy unrelated controls, all of Turkish origin. A clinical evaluation of all patients was accomplished applying the Brief Psychiatric Rating Scale (BPRS) test. The analysis of 5-HT2A receptor gene polymorphism was performed using the polymerase chain reaction technique. Results: Regarding 5-HT2A receptor gene polymorphisms, no statistically significant difference was found between schizophrenic patients and control subjects (p 1 0.05). There was no significant difference between the average of BPRS points of the patients and 5-HT2A receptor gene polymorphisms (p 1 0.05). Although there was no correlation between the duration of illness and polymorphism (p 1 0.05), the frequency of hospitalization was found to be higher in the patients with T/C and T/T genotypes compared with the patients with C/C genotype (p ! 0.05). Conclusion: Our findings indicate that the T102C polymorphisms of the 5-HT2A receptor gene does not play a substantial role in schizophrenia nor help evaluate susceptibility to schizophrenia. Since the 5-HT2A receptor gene polymorphism is associated with the frequency of hospitalization of the patients, it may be an indicator of prognosis in schizophrenia or help differentiate the patients who are somewhat refractory to antipsychotic treatment.