The location of the calcium-binding domain on protein kinase C is being addressed by mutational and structural studies. This work can be complemented by detailed studies of the properties of the binding of the enzyme to membranes. These binding studies have revealed a number of unique pieces of information about the properties of Ca(2+)-prompted membrane partitioning, including the fact that there is only one Ca(2+)-binding site which regulates the partitioning of the enzyme and that this site is located 0.3 nm from the membrane interface. Furthermore, the binding of protein kinase C to membranes has been shown to enhance the affinity of the enzyme for Ca(2+) by several orders of magnitude. We illustrate how contributions of the interactions of proteins with other molecules also affect the concentration of calcium required to affect membrane partitioning. Only when all of these factors are considered can a quantitative description of Ca(2+)-regulated protein binding to membranes be achieved. Thus conformational studies, together with classical thermodynamic studies, can provide a more detailed understanding of the functional, as well as, the structural, properties of amphitropic proteins.