A number of Palaeogene to Early Neogene gypsum units are located along the southern margins of the Ebro Basin (North-east Spain). These marginal units, of Eocene to Lower Miocene age, formed and accumulated deposits of Ca sulphates (gypsum and anhydrite) in small, shallow saline lakes of low ionic concentration. The lakes were fed mainly by ground water from deep regional aquifers whose recharge areas were located in the mountain chains bounding the basin, and these aquifers recycled and delivered Ca sulphate and Na chloride from Mesozoic evaporites (Triassic and Lower Jurassic). In outcrop, the marginal sulphate units are largely secondary gypsum after anhydrite and exhibit meganodules (from 0·5 to >5 m across) and large irregular masses. In the sub-surface these meganodules and masses are mostly made of anhydrite, which replaced the original primary gypsum. The isotopic composition (11·1 to 17·4‰ for δ18OVSMOW; 10·7 to 15·3‰ for δ34SVCDT) of secondary gypsum in this meganodular facies indicates that the precursor anhydrite derived from in situ replacement of an initial primary gypsum. As a result of ascending circulation of deep regional fluid flows through the gypsum units near the basin margins, the gypsum was partly altered to anhydrite within burial conditions from shallow to moderate depths (from some metres to a few hundred metres?). At such depths, the temperatures and solute contents of these regional flows exceeded those of the ground water today. These palaeoflows became anhydritizing solutions and partly altered the subsiding gypsum units before they became totally transformed by deep burial anhydritization. The characteristics of the meganodular anhydritization (for example, size and geometry of the meganodules and irregular masses, spatial arrangement, relations with the associated lithologies and the depositional cycles, presence of an enterolithic vein complex and palaeogeographic distribution) are compared with those of the anhydritization generated both in a sabkha setting or under deep burial conditions, and a number of fundamental differences are highlighted.