This study examined the association among knowledge of someone who has died from AIDS, cognitive functioning, and performance of protective health behaviors to reduce the risk of contracting HIV. Baseline data were analyzed from a sample of 229 injection drug users (IDUs) of heroin, a subset of the respondents from the Baltimore site of the International Neurobehavioral HIV Study. Multivariate logistic regression equations were fitted to predict risky injection drug use practices and sexual behavior based on cognitive performance scores and knowledge of someone who had died from AIDS. Among IDUs with lower cognitive reserves, knowing someone who had died from AIDS was associated with increased risk. This finding indicates that more intensive efforts may be required to reduce the risky behaviors among those IDUs with lower cognitive scores in higher risk social groups. Among IDUs with greater cognitive reserves, knowing someone who had died from AIDS was associated with decreased risk. This suggests that cognitive performance can provide protection to individuals in riskier social environments. These findings can aid in targeting HIV prevention efforts toward higher risk individuals within the IDU population.