Health literacy is related to a number of health status variables and has been associated with medication adherence in persons treated for HIV infection. Currently-available measures of health literacy require lengthy administration or have content or format limitations. In this paper we report the preliminary development and validation of a brief computer-administered health literacy test that includes content focused on medication adherence as well as questions based on a video simulation of an HIV-related clinical encounter. The measure shows significant relations with other measures of health literacy, HIV-related knowledge, and electronically-measured medication adherence. We also present receiver operating characteristic analyses that provide estimates of various scores' sensitivities and specificities so that the HIV-Related Health Literacy Scale can be used as a screening measure.