Background: The catechol-O-methyltransferase (COMT) Val ^108/158Met polymorphism of the dopamine system is essential for prefrontal cortex processing capacity and efficiency. In addition, dopaminergic neurotransmission is also associated with the sensory gating phenomenon protecting the cerebral cortex from information overload. It is however unclear if COMT genotype as a predictor of prefrontal efficiency modulates sensory gating on the level of the auditory cortex, i.e. the gating of the auditory evoked P50 and N100 components. Methods: P50 and N100 gating and COMT Val ^108/158Met genotype were determined in 282 healthy subjects of German descent carefully screened for psychiatric or neurological disorders. Results: A significant effect of the COMT genotype was observed for N100 gating (F. = 4.510, df. = 2, p. = 0.012) but not for P50 gating (F. = 0.376, df. = 2, p. = 0.687). Contrast analysis showed that Met/Met individuals had poorer N100 gating compared to Val/Met (F. = -12.931, p. = 0.003) and the Val/Val individuals (F. = -11.056, p. = 0.057). Conclusion: The results indicate that a high prefrontal efficiency as suggested by the COMT Met/Met genotype is associated with to a poor sensory gating of the N100 component. This would fit in a model where a high prefrontal processing capacity allows a pronounced afferent input of sensory information from the auditory cortex as reflected by a poor sensory gating. The more pronounced prefrontal contribution to the N100 compared to the P50 component may explain the exclusive genotype association with the N100 sensory gating. This preliminary model should be replicated and validated in future investigations.