Investigation of the copper-binding centre of Panulirus interruptus haemocyanin led to the discovery of a pseudo 2-fold axis relating two helical pairs surrounding and co-ordinating the two copper ions. The pseudo 2-fold symmetry relating one helical pair, co-ordinating Cu-A, to the second helical pair co-ordinating Cu-B is quite precise with 31 equivalent C α atoms having a root-mean-square deviation of only 1.47 Å. The 2-fold consists of a rotation of 174.6 ° and a translation parallel to the rotation axis of 0.7 Å. After superposition of the helical pairs, the two copper ions are within 1.1 Å and the three C α atoms of the histidine ligands of Cu-A are within a root-mean-square deviation of 1.0 Å from the C α atoms of the histidine residues co-ordinating Cu-B. Of the superimposed residues, 26% are identical in sequence. These data suggest that the current oxygen-binding centre of arthropodan haemocyanins is the result of dimerization, gene duplication and gene fusion of an ancestral mono-copper-binding helical pair. This suggestion is supported by the recent discovery that in the sequence of functional domains of molluscan haemocyanins only amino acid sequence homology with the arthropodan Cu-B helical pair has been found and no evidence for similarity with a Cu-A binding helical pair was observed. This provides strong evidence that a mono-copper-binding helical pair has been the ancestor of both the arthropodan and molluscan haemocyanins. Turning to the Fe-binding helical pairs in haemerythrins, it appears that they are less similar to each other than the two Cu-binding helical pairs in arthropodan haemocyanins. Nevertheless, the Fe-B haemerythrin helical pair superimposes well onto the Cu-A helical pair of Panulirus haemocyanin. A root-mean-square deviation of 1.9 Å for 24 equivalent C α carbon atoms is obtained, while Fe-B deviates 1.4 Å from Cu-A after superposition of the helices. Moreover, the three histidine ligands of the Cu-A helical pair are equivalent with three histidine ligands of the Fe-B pair. The structural similarity and correspondence in metal-binding ligands suggests that both haemocyanins and haemerythrins have originated from an ancestral mono-metal-binding helical pair having two ligands provided by the first helix and one ligand by the second helix. The Fe in the haemoglobin family is surrounded by two helices, each helix providing a histidine that is co-ordinating or approaching the metal ion. Although the similarity of the Fe-binding helical pair in the haemoglobins with the metal-binding helical pairs in haemocyanins and haemerythrins is less convincing than within the latter two classes of oxygen-binding proteins, it might be possible that all oxygen transport proteins are descendants from a primordial “metal-binding helical pair”.