The reported X-ray structure of horse-heart ferricytochrome c has been refined by conformational energy calculations, using a three-stage computational procedure. In stage I, the atomic positions are adjusted to conform to idealized bond lengths and bond angles characteristic of small amino acid derivatives, while yet remaining as close as possible to the X-ray coordinates. In stage II, atomic overlaps are eliminated by adjusting the backbone and side-chain dihedral angles to minimize the nonbonded energy, hydrogen-bonded energy, and rotational energy contributions. In the final stage of refinement, the electrostatic energy and a more accurate hydrogen-bonded energy treatment are considered, in addition to the energy contributions of stage II. A "fitting potential" of gradually decreasing strength is imposed in both stages II and III, in order to keep the computed structure as similar to the x-ray structure as is consistent with a low-energy conformation. The final computed structure of cytochrome c exhibits a very low conformational energy (-504 kcal/mol) and also closely resembles the X-ray structure (RMS deviation = 0.77 A for all atoms). However, a special treatment was required in order to alter the location of the phenyl ring of phenylalanine-82. In contrast to the originally published X-ray structure, which shows the phenyl ring pointing away from the heme, the phenyl ring in the computed structure is tucked into the heme crevice, in a position similar to that observed in the reduced form of tuna cytochrome c, in the oxidized form of Rhodospirillum rubrum cytochrome c2, and also in the recently determined structure of oxidized tuna cytochrome c.