We present a new analysis of Fe-57 isotropic hyperfine coupling constants in iron-sulfur clusters containing one, two, three, or four iron atoms. Instead of relying on a unique set of site values for ferric and ferrous ions which depend on the degree of covalency of the iron atom with the surrounding atoms and which contain a variable spin-orbit contribution, we propose the use of semi-empirical free ion constants (a) over bar(Fe3+) and (a) over bar(Fe-2.5+) whose values are semiempirically found to be about -31 MHz and -32 MHz respectively (we found, in addition, -38 MHz for the pure core-polarization constant (a) over bar(c)(Fe2+), in excellent agreement with theoretical calculations). These are transferrable from one system to another, and can be combined with estimated covalency factors to define "site values." These values allow us to derive a set of spin projection coefficients for a variety of iron-sulfur clusters (two to four irons, and some mixed-metal complexes) in different oxidation states, These can be compared to those deduced from proposed spin-coupling schemes. For the [Fe4S4](3+) cluster, which forms the active site of the high potential iron protein (HiPIP), we conclude that the best simple spin state, within a pairwise model in which two ions dimers combine to make a tetramer, is (S-mv,S-,S-ferric,S-t] = 7/2,3,1/2], and not 9/2,4,1/2) as is often assumed. The stabilization of this spin state is rationalized in terms of spin frustration. For Fe-4 ferredoxins, we find spin projection coefficients intermediate between those of the 7/2,3,1/2 and 5/2,2,1/2] states, whereas the aconitase cluster (both with and without substrate) has coefficients intermediate between those of the states 9/2,4,1/2] and 7/2,3,1/2). In aconitase, the change upon release of substrate appears to be accompanied by,a relocalization of the mixed-valence pair. We also report analyses for mixed-metal complexes of the form [MFe(3)S(4)](n+), with (M,n) = (V,2), (Co,2), (Ni,1), (Zn,1), and (Mo,3), in an attempt to gain some insight into a wide variety of polynuclear spin-coupling schemes.