Objective: To investigate the association between catechol-O-methyl transferase {COMT) Vall58Met polymorphism and prepulse inhibition of the auditory startle reflex ( PPI) in patients with schizophrenia. Methods: Totally 178 patients with schizophrenia and 190 healthy volunteers were recruited. The auditory startle reflex was detected by using SR-HLAB monitoring system. The indexed of the auditory startle reflex included the amplitude, habituation% and PPI30, PPI60, PPI120 (the lead interval was set 30 ms, 60 ms, 120 ms). COMT Vall58Met polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP). The differences of PPI among COMT genotypes were compared. Results: Compared to the healthy volunteers, patients with schizophrenia had a significant lower the amplitude of auditory startle reflex[(563 ±460) mV vs (695 ±447) mV, P <0. 05] and habituation% [ (32 ±46) vs (48 ± 33), P < 0. 01] as well as the % PPI120[(27 ±5) vs (35 ±3), P <0. 05]. The significant differences in COMT allelic and genotypic distribions were observed between patients with schizophrenia and healthy volunteers =8. 16,11. 74, Ps <0. 05). The significant main effect of COMT genotype on habituation% was observed (P < 0. 05) but no interaction genotype by diagnosis on the amplitude of auditory startle reflex, habituation% and % PPI120 was observed (Ps > 0. 05). Conclusions: There may be a correlation between COMT genotype and adaptability, but not between COMT genotype and PPI deficit present in patients with schizophrenia. [ABSTRACT FROM AUTHOR]