Numerous studies have evaluated event-related potentials (ERPs) as biological indicators of the liability for alcoholism. This study extends that approach by investigating ERPs in boys at risk for other substance use disorders. Prepubertal (10-12 years) sons of fathers diagnosed with psychoactive substance dependence (n = 28) were compared to matched sons of nonaffected fathers (n = 26) on an auditory ERP oddball task. Multivariate analyses of variance applied to peak amplitude and latency measures indicated small to moderate between-groups differences at midline or parietal sites: N2 and P3 amplitude; P2, N2, P3, and Nc latency. This replicated P3 amplitude findings in alcoholism-risk studies, though the effect size was moderate. Analysis of event-related alpha power indicated significantly longer latency of alpha synchronization and oscillations of desynchronization in boys at risk. The alpha power findings were statistically the more robust of the measures applied. The role of neurocognitive factors in determining liability for substance use disorders is discussed.