Lysis of infected cells by CD8⁺ T cells is an important mechanism for the control of virus infections, but remains difficult to quantify in vivo. Here, we study the elimination kinetics of viral antigen‐positive lymphocytes by antiviral CD8⁺ T cells using flow cytometry and mathematical analysis. In mice acutely infected with lymphocytic choriomeningitis virus, more than 99.99 % of target cells were eliminated each day, corresponding to a half‐life of 1.4 h. Even in mice exposed to virus 300 days previously, and with no ex vivo killing activity, 84 % of the target cells were eliminated per day. Unexpectedly, the elimination kinetics of antigen‐positive lymphocytes was not significantly impaired in mice deficient in either perforin‐, CD95 ligand‐ or TNF‐mediated cytotoxicity. For viruses with a particular tropism for lymphocytes, such as Epstein‐Barr virus or HIV, our results illustrate how effectively CD8⁺ T cell‐mediated elimination of target cells can potentially contribute to virus control and immunosuppression.