On the basis of a simple model of 1:1 complex formation between planar molecules, this equation was derived: △G°u = A(G°SL — G°MS —G°ML),where △G°u is the standard unitary free energy change for complex formation, A is the area of overlap in the plane-to-plane interaction between the two molecules, and G°IJ is a free energy of interaction per unit area between I and J (S, L, and M represent substrate, ligand, and medium.) If the parenthesized term is roughly constant for a series of substrates and ligands in a constant medium, it is suggested that the quantity G°SL does not play a major role, and that the complex stability is primarily con-trolled by repulsive solvent interaction terms (G°MS and G°ML). It follows that the system will assume an orientation of S and L such as to maximize A. Therefore, maximal overlap areas were estimated for 18 neutral and 32 ionic complexes. A substantial improvement in the area correlation was obtained, and the observation was made that there is no significant difference between the average behavior of neutral and charged complexes. The maximal overlap concept provides a general “first-order” description of molecular complex formation in aqueous solution. Deviations from the line are significant and may be associated with specific structure-stability relationships. Application of the maximal overlap approach leads to average complex structures without introducing arbitrary assumptions about specific group interactions. The structures thus generated are consistent with the chemical reactivity of the complexes.