Density functional theory geometry optimizations and reduction potential calculations are reported for all five known oxidation states of [Fe(4)S(4)(SCH(3))(4)](n)()(-) (n = 0, 1, 2, 3, 4) clusters that form the active sites of iron-sulfur proteins. The geometry-optimized structures tend to be slightly expanded relative to experiment, with the best comparison found in the [Fe(4)S(4)(SCH(3))(4)](2)(-) model cluster, having bond lengths 0.03 A longer on average than experimentally observed. Environmental effects are modeled with a continuum dielectric, allowing the solvent contribution to the reduction potential to be calculated. The calculated protein plus solvent effects on the reduction potentials of seven proteins (including high potential iron proteins, ferredoxins, the iron protein of nitrogenase, and the "X", "A", and "B" centers of photosystem I) are also examined. A good correlation between predicted and measured absolute reduction potentials for each oxidation state of the cluster is found, both for relative potentials within a given oxidation state and for the absolute potentials for all known couples. These calculations suggest that the number of amide dipole and hydrogen bonding interactions with the Fe(4)S(4) clusters play a key role in modulating the accessible redox couple. For the [Fe(4)S(4)](0) (all-ferrous) system, the experimentally observed S = 4 state is calculated to lie lowest in energy, and the predicted geometry and electronic properties for this state correlate well with the EXAFS and Mössbauer data. Cluster geometries are also predicted for the [Fe(4)S(4)](4+) (all-ferric) system, and the calculated reduction potential for the [Fe(4)S(4)(SCH(3))(4)](1)(-)(/0) redox couple is in good agreement with that estimated for experimental model clusters containing alkylthiolate ligands.