ALTHOUGH many peptides are generated during the intracellular processing of protein antigens, only a few are selected for recognition by the immune system(1-5). The immunodominant epitope of hen egg white lysozyme (HEL) for H-2(k) mice is contained in a tryptic fragment of amino-acid residues 46-61 (refs 6, 7). The core of this T-cell epitope, from amino acids 52 to 61 (DYGILQINSR), contains those residues required for binding to the class II molecule I-A(k) (ref. 7). Most of the naturally processed fragments recovered from I-A(k)-bearing antigen-presenting cells (APCs) cultured with HEL contained this 52-61 core sequence, presented as a nested set of peptides with extensions at both the amino and carboxyl termini(8). We now compare the handling by APCs of peptides containing HEL 52-61 to establish whether there is an advantage for the APC in selecting extended peptides : different complexes between peptides and major histocompatibility complex (MHC) molecules varied greatly in the amount of time associated with the APC, and in their immunogenic strength. This difference in persistence is one of the factors contributing to the selection and immune recognition of peptide-MHC complexes by T cells.