An important challenge for the large-scale production of cellulosic ethanol is the development of efficient cellulase enzymes on an industrial scale. However, specific details of the interaction between cellulase enzymes and their substrates are not yet understood. Although the structure of cellulase from several organisms has been determined and provides some insight into the process of saccharification, there is a need for experimental measurements to explain macroscopic observations such as the resistance to cellulase activity of some fractions of cellulosic biomass and to understand the properties of natural cellulose that influence the enzymatic hydrolysis process. In this talk we describe our measurements of the enzymatic hydrolysis process obtained in situ, and with high spatial resolution. The microcrystalline cellulose we have chosen as a substrate was derived from wood pulp and is expected to be similar to the crystalline components of cellulose from biomass sources that are candidates for ethanol production. Sequences of atomic force microscope (AFM) images at a single location and spaced at regular time intervals enabled measurements of hydrolysis rates on individual cellulose microfibrils both individually and when part of a fibril bundle as a function of time. Our work appears to be the first to describe the time resolved interaction of cellulose with cellulase at high spatial resolution.