A prominent feature of HIV infection is a progressive anergy of T cells and an increase of activation-dependent T-cell death. CD80 (B7.1), the ligand of CD28, is an important co-stimulatory molecule on antigen-presenting cells that delivers an essential second signal for T-cell activation. To test whether immunologic dysfunction in HIV disease involves CD80, we studied CD80 expression on circulating monocytes in heparinized whole blood of 33 HIV-infected patients and 13 controls. Most monocytes in patients and controls expressed significant amounts of CD80. There was no statistical difference of mean fluorescence intensity (MFI) of CD80 expression when all HIV-infected patients were compared with healthy controls. However, asymptomatic patients in clinical Centers for Disease Control and Prevention (CDC) stage A showed a significantly stronger CD80 expression than did healthy controls. Additionally, patients receiving antiretroviral therapy exhibited significantly higher CD80 expression than did patients not receiving therapy and healthy controls. We did not find a correlation with the presence of HIV p24 antigenemia and counts of CD4+ and CD8+ T cells. Although we studied CD80 expression only on circulating monocytes and not in HIV-infected monocytes or in activated macrophages, our data do not support a role for a general impairment of CD80 expression in induction of anergy in HIV disease.