Three closely related rhombohedral crystal structures of human annexin V have been analysed and compared: a low-calcium, a high-calcium and an ytterbium-soaked crystal. The occupancy of the calcium sites increases at higher calcium concentrations, but the calcium is removed rather than replaced during soaking in the ytterbium solution. Instead, other sites are substituted at high calcium concentrations as well as in the presence of ytterbium. Furthermore, a new site is revealed in the ytterbium-soaked crystal which may give a clue to the mechanism of conformational change that takes place in the third domain of annexin V in the presence of very high calcium concentrations and of phospholipids.