During double stranded DNA phages morphogenesis, the icosahedral symmetry of the head is interrupted by a unique portal vertex defined by the presence of a single protein arranged as a dodecameric ring. This oligomer in P22, as in other phages, connects the head to the tail complex of these phages and is known as portal protein. In the case of P22 bacteriophage, the portal protein is a dodecamer and each subunit has 84 kDa. The assembly process of the monomeric portal proteins of different bacteriophages into rings has been addressed in previous studies. In a recent study from our group, the in vitro unfolding/refolding processes of the portal protein of P22 bacteriophage was investigated at different temperatures (1, 25 and 37 ^oC) through the use of urea and high hydrostatic pressure (HHP) and we have observed the existence of two intermediate species with high propensity to form aggregates. In the present study, we are evaluating the stability of the dodecameric species of P22 portal protein. In a first moment we could observe that, as suggested by other authors, the formation of the dodecameric structure seems to confer a higher stability to the protein which becomes much more pressure-resistant, being only partially dissociated when pressure up to 3.2 kbar was combined to low temperatures (1^oC) or in the presence of very low salt concentrations. Surprisingly, when urea-induced denaturation was performed; the dodecamers were totally dissociated into monomers with less than 1M urea. These results suggest that the structure of the dodecameric portal protein is maintained mainly by strong interactions such as hydrogen bonds, which can not be accessed by HHP.