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The P300 amplitude of the event-related potential as a mediator of the association between parental substance use disorder (SUD) and child's neurobehavioral disinhibition was assessed. The P300 amplitude was recorded using an oddball task in sons of fathers having either lifetime SUD (n = 105) or no psychiatric disorder (n = 160). Neurobehavioral disinhibition was assessed using measures of affect regulation, behavior control, and executive cognitive function. Parental SUD and child's P300 amplitude accounted for, respectively, 16.6% and 16.8% of neurobehavioral disinhibition variance. Controlling for parental and child psychopathology, an association between parental SUD and child's P300 amplitude was not observed. It was concluded that the P300 amplitude does not mediate the association between parental SUD and child's neurobehavioral disinhibition.