The P300 event-related potential (ERP) is sometimes larger for individuals at low- compared to high-risk for alcoholism. These effects are inconsistent, and how P300 is affected by tobacco smoking in the context of alcoholism risk is unknown. The present study used P300 to examine the inter-relationship between alcoholism heritability and smoking status.P300 was elicited with a visual discrimination task from young adults at low- and high-risk for alcoholism. Half of the subjects in each risk category reported that they did not smoke cigarettes, and the other half reported that they smoked regularly, with equal numbers of male and female subjects assessed. ERPs were recorded, and subjects were instructed to respond only to an infrequently presented target stimulus that occurred in a series of standard and distracter stimuli.P300 amplitude from the target stimuli was larger for the low-risk compared to high-risk subjects overall. However, smoking status demonstrated even stronger effects, with non-smokers producing consistently larger component amplitudes than smokers and accounting for more variance than alcoholism risk. These group factors also significantly affected P300 scalp topography. No reliable alcoholism risk or smoking group effects were obtained for the ERPs from the other stimuli.The findings suggest that P300 measures of alcoholism risk in young adults are moderated by smoking status. Theoretical implications are discussed.