It is widely accepted that the preeminent technique for the determination of the structure of biological macromolecules is X-ray crystallography. For the solution of structures at near atomic resolution, it has for many years been the only technique, although recently a number of structures of low molecular weight (< 25000) have been solved by NMR. A handful of structures has also been investigated at high resolution by neutron crystallography, but in these cases the X-ray structure was already known and neutrons were used to obtain complementary information on the positions of important protons in the macromolecule or on the surrounding water molecules. Despite the success of the X-ray techniques, there exist, however, a number of cases, in particular of large macromolecular assemblies, where high resolution information cannot be obtained for at least part of the structure even though highly diffracting crystals exist. It is often one particular chemical component or part of a molecule that cannot be seen with X-rays. This is usually due to the fact that these components are at least partially disordered in the crystal. Some examples are the nucleic acid in spherical viruses, the DNA in nucleosome core partkles, the lipid in lipoproteins and detergent in crystals of detergent solubilized membrane proteins.