Cytochromes P450 play a key role in drug metabolism in man. Electrons are supplied to the cytochromes by NADPH through the flavoprotein NADPH-cytochrome P450 reductase (CPR). CPR is made up of three domains, and domain movement is essential for the activity of the enzyme. We have evidence from NMR and SAXS that CPR exists in an equilibrium between a compact and an extended conformation, each playing a specific role in the catalytic cycle. Interpretation of the SAXS data is complicated by partial reduction of the enzyme during the experiment. We therefore plan to use SANS to study each of the catalytically relevant redox states of CPR and of three mutants. This will allow us to determine low-resolution structures of the compact and extended states (to be refined by NMR data) and to determine the position of the equilibrium in each of the catalytically relevant states.