Since each major histocompatibility complex (MHC) molecule can bind many different peptides, it might be predicted that competition for the same MHC-binding site takes place between peptides with unrelated sequences. As Luciano Adorini and Zoltan Nagy report here, this does indeed occur, both in vitro and in vivo. In-vivo competition between peptides for antigen presentation to T lymphocytes is an important influence on the immunodominance of T-cell determinants. In addition, it is possible to modulate T-cell activation by interfering with the binding of antigenic peptides to MHC class II molecules. This could represent a suitable approach to a rational treatment of autoimmune diseases and, possibly, of allograft rejection.