The aim of this study was to evaluate the changes and the correlations between the main lymphoid phenotypes indicative of activation and/or functional states during the course of HIV infection. Immunophenotype studies by flow cytometry were performed on blood samples from 59 HIV-1-positive patients, divided into four stages, and 18 seronegative healthy controls, to determine the expression of HLA-DR, CD29 and CD45RA on CD4+ and CD8+ lymphocytes. HLA-DR expression was elevated on the total lymphocyte population and in both the main T subsets. Its presence on CD4+ lymphocytes probably has a different significance in the first phase of infection when it is indicative of reactive activation, in contrast to the more advanced stages of disease when it favors the spread of HIV infection among this cellular subset. The increasing state of immune activation is also confirmed by a proportional decrease in the expression of CD45RA, substantial stability of CD29 and an increase in double-negative CD4+ cells as the infection proceeds. Also CD8+HLA-DR+ lymphocytes increase during the course of disease. The parallel increase of the CD8+CD45RA+ subset in asymptomatic patients suggests the presence in this phase of infection of peripheral blood immature and activated CD8+ cells. Similarly to CD4+, the CD29 subset of CD8+ lymphocytes remains unchanged compared to controls during disease progression. In both CD4+ and CD8+ subsets we observed the increase of a double-negative sub-population of uncertain significance. HLA-DR, the memory marker CD29 and the naive marker CD45RA seem to be the more promising and helpful indicators for a better staging of disease and may provide information that accurately correlates with progression of infection. The peculiar trend of the described phenotypic alterations could represent changes in the immune response to HIV during disease progression and facilitate the definition of specific immune patterns in different stages of HIV infection.