Entry into the cell cycle represents a fundamental step before generating an effector immune response. The relationship between the cell cycle and antigen‐driven T cell response remains, however, poorly understood in virus infection, including HIV. We have identified a critical fraction of CD4⁺CD45RO⁺ memory T lymphocytes that express the Ki67 antigen in chronically HIV‐infected patients. A high accumulation of Ki67 protein is detected in CD4⁺CD45RO⁺Ki67⁺ cells that are in the G1 phase of the cell cycle (92 ± 5 %) but not in S and G2 + M phases, in contrast to normal individuals. Of these cells, 20 – 60 % are spontaneously producing IL‐2 and IFN‐γ, unlike CD4⁺CD45RO⁺ that do not express Ki67. In addition, HIV‐p24 antigen is detectable only in a small fraction CD4⁺Ki67⁺ cells. In conclusion, CD4⁺Ki67⁺ lymphocytes are circulating effector cells accumulated in the G1 phase of the cell cycle and may be involved in the immune surveillance during HIV infection.