Recent advances in technology have led to the realization that the populations of naive T cells specific for different foreign peptide:MHC (p:MHC) ligands vary in size. This variability is due, in part, to the fact that certain peptides contain amino acids that engage in particularly favorable interactions with TCRs. In addition, deletion of clones with cross-reactivity for self-p:MHC ligands may reduce the size of some naive populations. In many cases, the magnitude of the immune response to individual p:MHC epitopes correlates with the size of the corresponding naive populations. However, this simple relationship may be complicated by variability in the efficiency of T cell recruitment into theimmune response. The knowledge that naive population size can predict immune response magnitude may create opportunities for production of more effective subunit vaccines.