Within the past few years a new technique for surface studies has been introduced which is capable of atomic resolution. This method involves positioning a probe a few angstroms from the surface of interest. A small potential is applied across the gap and the electron tunneling current is measured. The probing tip is then scanned across the surface in two dimensions while adjusting the distance between the tip and surface to maintain a constant current. In this way the tip is made to follow the contours of the surface. The real space resolution obtained in this way is about 3A parallel to the surface and O.l A in the surface normal. The objective of the proposed research program is to develop a Scanning Tunneling Microscope (STM) for the study of biological macromolecules at high resolution under ambient conditions. The development plan includes the design, construction and demonstration of an STM system. Various substrates such as highly-ordered pyrolytic graphite (HOPG) will be explored to demonstrate that atomically flat regions of sufficient size exist for the study of biological macromolecules and that these surfaces can be modified with surfactant monolayers to enable the study of aqueous systems. The capability of the STM will be tested using model enzymes such as lysosome, ribonuclease, and carbonic anhydrase. It is proposed to explore the mechanism by which electron transfer occurs from the tip through the solvent to atoms which lie on the exterior of the macromolecule, and the mechanism of electron conduction from the surface of the macromolecule to the substrate.