In recent years, audio computer-assisted self-interviews (ACASI) have been demonstrated to increase and presumably improve the quality of drug reporting in epidemiologic research. Surprisingly little research is available, however, regarding the potential limitations of this technique. For example, it is unclear what effects computer literacy may have on the validity of substance use information collected via ACASI. Respondents with limited computer skills may become distracted by the automated technology, requiring the devotion of considerable cognitive effort to the navigation of unfamiliar computer equipment and software that would otherwise be available for use to more carefully process and answer survey questions. In this study, we report findings from a community ACASI survey conducted in Chicago, which are used to address this problem. Using multiple indicators of computer literacy, a covariance structure model was developed to test the hypothesis that persons with low computer literacy skills may report drug use with less accuracy. Biological assays were used to evaluate 30-day cocaine use reporting accuracy. Model findings confirmed a positive relationship between computer literacy and the accuracy of cocaine use reports. Future research should investigate strategies for improving the usability of self-administrated computer reporting systems for persons with little direct computer experience.