To investigate the changes of CD28 and HLA-DR molecules on CD4(+) and CD8(+) T cells during HIV infection, we classified 130 HIV-infected Koreans into four groups by the CD4 level as follows: group I (greater than or equal to500 cells/mm(3) ), group II (201-499 cells/mm(3) ), group III (51-200 cells/mm(3) ), and group IV (less than or equal to50 cells/mm(3) ). In CD4(+) T cells, the proportion of CD28 expression decreased significantly with the CD4 level while the proportion of HLA-DR expression increased gradually. In particular, the changes of HLA-DR expressions on CD4(+) T cells were parallel to the loss of CD28 molecules from stage III to IV. However, the CD28 expression on CD8(+) T cells decreased dramatically in the early stage of HIV infection, and the sum and pattern of CD28 and HLA-DR expressions on CD8(+) T cells was stable after the first stage. Even though CD28 down-regulation on CD8(+) T cells was very severe from the early stage of HIV infection, it might not influence the survival time of HIV-infected Koreans. The sum of the CD28(+) subsets and HLA-DR subsets in each T cell was stable in all stages of disease progression. The sums of the CD28(+) subsets and HLA-DR+ subsets in CD4(+) T and CD8(+) T cells were constant as approximately 100% and 55-60% of each T cell. These results suggested that the changes of CD28/HLA-DR expressions on CD4(+) T cells were more predictable than those on CD8(+) T cells in the evaluation of the disease progression during HIV-infected periods. However, we need further studies to understand why the sum of two molecules in each T cell are constant.