Objective: To evaluate the PON1 and COMT genetic polymorphisms and their relationship with the symptoms of schizophrenia and the response to antipsychotic treatment. Material and method: 46 inpatients with schizophrenia were psychiatrically and scalar evaluated and DNA analysis was performed. Results: The PON1 promoter mutation was associated with a good response to atypical antipsychotics (p=0.012). The Val108/158 Met COMT mutation was related to the intensity of negative symptoms (p=0.045). The COMT promoter mutation was associated to a lower intensity of positive symptoms (p=0.045). The 408 G/C COMT gene polymorphism was isolated in premiere. Conclusions: Our study suggests that mutations of the PON1 gene predict response to the antipsychotic treatment. Our findings confirm the role of the COMT gene in the clinical picture of schizophrenia. The existence of COMT genetic polymorphism Leu86 is firstly described in literature.