To determine if the P300 component of the event-related potential indexes risk for substance use and related disorders, we presented a community sample of 377 16–18-year-old males a visual oddball task and selected 31 subjects with the smallest and 31 subjects with the largest P300 amplitudes. An additional 31 subjects whose amplitudes fell in the middle of the amplitude distribution were assigned to the average group. The small and average amplitude groups were more likely to have alcohol dependence and more symptoms of alcohol dependence than the large amplitude subjects. The small amplitude group had more symptoms of illicit drug dependence than the other groups. There was also a significantly larger proportion of subjects with externalizing disorders in the small amplitude group than in the large P300 group. These findings suggest that P300 amplitude may index a spectrum of risk for disinhibited psychopathology.