Aqueous two-phase systems have been used to study the human red cell during metabolically induced shape changes. When the discoid character of the cells was lost in favour of echinocytic forms, the partition increased both in charge-sensitive and in charge-insensitive two-phase systems. Reversal of the shape transformation by ATP repletion not only led to shape recovery but also restored the initial partition. Therefore it is apparent that red cells exhibit a shape-dependent partition behaviour. As the partition is dependent on surface properties (such as charge and hydrophobicity) of the partitioned material, the results show that the shape changes caused rearrangement of the membrane and thereby exposure of or greater accessibility of binding groups on the cell surface. The similar partition behaviour in the charge-sensitive and charge-insensitive phase systems show that the increased partition was caused mainly by increased hydrophobic interactions between the cells and the upper phase. The observed partition behaviour therefore suggests that the echinocytic cells acquire a higher affinity for the upper phase by repacking the lipid bilayer or at least the outer leaflet into a less efficient packed and thus more fluid structure.