A practical method is presented for calculating the dependence of electron transfer rates on details of the protein medium intervening between donor and acceptor. The method takes proper account of the relative energetics and mutual interactions of the donor, acceptor, and peptide groups. It also provides a quantitative search scheme for determining the important tunneling pathway(s) [specific sequence (s) of localized bonding and antibonding orbitals of the protein which dominate the donor-acceptor electronic coupling] in native and tailored proteins, provides a tool for designing new proteins with prescribed electron transfer rates, and provides a consistent description of observed electron transfer rates in existing redox labeled metalloproteins and small molecule model compounds. © 1990 American Institute of Physics.