Using monoclonal antibodies against CD45, CD45RA, CD45RB, and CD45RO, the surface density of expression and proportions of different CD45 isoforms were analyzed on CD4 + and CD8 + T lymphocyte subsets in HIV + patients and controls. Analysis of the relative specific fluorescence (RSF) of CD45 isoforms showed a significant reduction in expression of total CD45 and its isoforms, CD45RA, CD45RO, and CD45RB, on CD4 + and CD8 + lymphocyte subsets in HIV + patients compared with controls. However, expression of phosphotyrosine in the cytoplasm of CD4 + and CD8 + lymphocytes did not differ significantly between HIV + patients and controls. Percentages of “naive” CD45RA + RO − CD4 + and CD8 + lymphocytes were lower than control values in all HIV + patients (P< 0.001). Compared with controls, HIV + patients had similar percentages of “memory” CD45RA − RO + CD4 + lymphocytes but significantly higher percentages of memory CD8 + lymphocytes (P< 0.001). Percentages of memory CD8 + lymphocytes were lowest in patients with AIDS (P< 0.001). The consistent reduction in surface expression of all CD45 isoforms observed in our study may be of relevance to the impaired T cell activation characteristic of HIV infection. Also, our results argue against the selective depletion of memory CD4 + lymphocytes in HIV-induced disease.