Cytotoxic T-cells recognise small peptides (8-10 amino acids) complexed to MHC class I molecules. These peptides are derived from endogenous cytosolic proteins that are degraded and delivered to the nascent MHC class I molecule within the endoplasmic reticulum (ER). Targeting gene products directly to the ER (by the addition of an amino-terminal insertion sequence) should thus enhance CTL responses. This was successfully demonstrated using recombinant vaccinia viruses expressing influenza proteins, but the principle should also be applicable to DNA vaccines. Targeting antigens for intracellular degradation (and thus entry into the MHC class I pathway) by the addition of ubiquitin signal sequences, or mutation of other signal sequences, was shown to be effective at increasing CTL responses.