The Z variant of ₁-antitrypsin (Z-AT) is present in 4% of North Europeans and is associated with liver cirrhosis and emphysema. Polymers accumulate within the hepatocyte and the subsequent plasma deficiency of AT renders the lungs susceptible to proteolysis and early onset emphysema. We have previously demonstrated that the Phe-Leu-Glu-Ala-Ile-Gly (6mer) peptide specifically binds to Z-AT and inhibits polymerisation. Here we present the first detailed biochemical study of the purified Z-AT-6mer binary complex. Biochemical studies indicated that this complex was inactive as a proteinase inhibitor and the peptide annealed to -sheet A of Z-AT. Removal of the N-acetyl terminus of the 6mer peptide did not affect the peptide's ability to prevent polymer formation. However, the non-acetylated 6mer-Z-AT complex dissociated at a rate 2.75 times faster than the acetylated 6mer-Z-AT complex to yield an active inhibitor; K_off 5.5 ± 1.07 vs 2.0 ± 0.25 10⁶ s^-1 respectively. These biochemical data indicate a potential therapeutic approach whereby polymerisation is prevented in the liver, with the gradual release of the peptide from the binary complex restoring proteinase inhibitory function within the tissues. Thus, it raises the novel prospect of ameliorating both the cirrhosis and the emphysema associated with Z-AT.