Abstract : The Callovo-Oxfordian clay formation selected to host the French underground laboratory for nuclear waste disposal studies covers a mineralogical transition between two illite/smectite mixed layered minerals. The first one, randomly interstratified (R0), is present in the upper part of the borehole, whereas the other one having an ordered stacking (R1) is present in the deeper part of the series. Both the retention properties of the formation and the reactivity of these minerals in response to a storage-induced physico-chemical perturbation are influenced by clay mineralogy. Usual simplified identification methods described in the literature are shown to be ineffective for accurate clay mineral characterization. Instead, direct comparison between calculated and experimental X ray diffraction diagrams recorded for the same sample after different treatments was used. The structural model was validated if all characteristics (peak positions, intensity ratios, peak profiles) of the experimental traces were successfully reproduced with a unique model. Clay minerals from drill-hole EST104 are described as a mixture of three main phases: illite, smectite and a randomly interstratified illite/expandable mixed layer having a fixed composition (35% exp.). No structural evolution was observed with depth, and the observed mineralogical transition results from contrasting proportions of the different phases. The present results are not consistent with diagenetic illitization processes commonly described in the literature for clay-rich sediments. However, very similar results were obtained by using our methodology on samples from a typical diagenetic series. These original results imply to reconsider the reaction mechanisms proposed for these minerals and their kinetic modeling. Finally, the reactivity of clay minerals from the Callovo-Oxfordian series in response to an alkaline perturbation is very limited because organic matter covers clay particles shielding their reactive sites.