The lymphocyte subset expressing the gamma delta T cell receptor is increased in several infectious diseases including HIV infection. In this study the expression on gamma delta lymphocytes of the T cell activation markers CD25, HLA-DR and CD38, as well as the two isoforms of CD45, namely CD45RA and CD45RO, was determined in the peripheral blood of 56 HIV-infected intravenous drug users and 34 HIV-seronegative blood donors by two-colour flow cytometry. The percentage of gamma delta lymphocytes expressing HLA-DR and CD38 was higher than those in HIV-seronegative controls (P < 0.001 and P < 0.0001, respectively). Furthermore the HLA-DR+gamma delta+ lymphocytes correlated inversely with CD4+ T lymphocyte absolute count (P < 0.02 for both). The levels of gamma delta lymphocytes expressing CD25, CD45RA and CD45RO were similar to those in HIV-seronegative controls. Activated gamma delta lymphocytes may play a role in the HIV disease process and could provide a useful marker for disease progression.