This paper reports the initial results of a pilot study to evaluate the acceptability and effectiveness of a program to enhance health literacy in low-income HIV-infected Latino men and women receiving antiretroviral therapy. Participants rated the program highly on measures of satisfaction, providing evidence of its acceptability. The effectiveness of the program was assessed in comparisons of the intervention (n = 41) and standard care only (n = 40) groups at baseline and 6-week intervals. Program participants showed significant improvement over comparison group participants on measures of HIV/AIDS and treatment-related knowledge and recognition and understanding of HIV terms. Although there were no significant changes in adherence mastery and behaviors during the 6-week follow up period, there were significant changes in program participants' knowledge about medication adherence. Future steps to examine the sustainability of the program in the medical management of patients are planned in addition to determining its long-range relative impact.