The de novo design of di-iron proteins is an important step towards understanding the diversity of function among this complex family of metalloenzymes. Previous designs of due ferro (DF) proteins have resulted in tetrameric and dimeric four-helix bundles having crystallographically well-defined structures and active-site geometries. Here, the design and characterization of DFsc, a 114 residue monomeric four-helix bundle, is presented. The backbone was modeled using previous oligomeric structures and appropriate inter-helical turns. The identities of 26 residues were predetermined, including the primary and secondary ligands in the active site, residues involved in active site accessibility, and the gamma beta gamma beta turn between helices 2 and 3. The remaining 88 amino acid residues were determined using statistical computer aided design, which is based upon a recent statistical theory of protein sequences. Rather than sampling sequences, the theory directly provides the site-specific amino acid probabilities, which are then used to guide sequence design. The resulting sequence (DFsc) expresses well in Escherichia coli and is highly soluble. Sedimentation studies confirm that the protein is monomeric in solution. Circular dichroism spectra are consistent with the helical content of the target structure. The protein is structured in both the apo and the holo forms, with the metal-bound form exhibiting increased stability. DFsc stoichiometrically binds a variety of divalent metal ions, including Zn(II), Co(II), Fe(II), and Mn(II), with micromolar affinities. 15N HSQC NMR spectra of both the apo and Zn(II) proteins reveal excellent dispersion with evidence of a significant structural change upon metal binding. DFsc is then a realization of complete de novo design, where backbone structure, activity, and sequence are specified in the design process.