We determined equilibrium constants for the binding of 16 peptides (based on four T cell epitopes) to three MHC class I proteins (A2, Kb, and Ld) on intact cells and estimated the number of accessible peptide-binding sites on these cells. From these results, and the concentrations of peptides required to sensitize target cells for lysis by CD8+ CTL, we conclude that the critical number of peptide-MHC complexes required per target cell for the activation of CTL responses varies with different combinations of peptide-MHC complexes and CTL clones from several thousand complexes to fewer than ten per target cell.