THE interaction of a biologically active substance with a selective receptor (for instance, substrate and enzyme) to cause a certain physiological effect is chemically complex, requiring not only a certain minimum of steric congruity of the molecules but also a given electron density distribution in the interacting functional centres. If either of these requirements is not satisfied, the reaction will either not take place at all or its effectiveness will be diminished by several orders of magnitude. It is thus important to discover the limits of steric and electronic matching, both in the rational search for substances with similar, modified or antagonistic action, and to understand the underlying mechanism.