Strong memory T cell responses result partly from the selection of Ag-specific clones during immunization. In this study, we show that a monoclonal CD8 T cell population expressing a unique TCR is heterogeneous in terms of clonogenic potential following activation under optimal conditions. More importantly, the frequency of clonogenic cells is strongly increased among Ag-experienced cells, indicating that these cells were either generated or selected during the in vivo primary response. Moreover, strong proliferative responses of primed cells result from this enhanced frequency, as proliferating naive and primed cells display the same cycling parameters, i.e., lag time and intermitotic interval. Hence, these results suggest that the clonogenic potential of individual cells is imprinted before Ag encounter and that clonogenic precursors are selected or generated following in vivo activation.