Conventional x-ray diffraction topography is currently used to map defects
in the bulk of protein crystals, but the lack of sufficient contrast is fre
quently a limiting factor. We experimentally demonstrate that this barrier
can be circumvented using a method that combines phase sensitive and diffra
ction imaging principles. Details of defects revealed in tetragonal lysozym
e and cubic ferritin crystals are presented and discussed. The approach ena
bling the detection of the phase changes of diffracted x rays should prove
to be useful in the study of defect structures in a broad range of biologic
al macromolecular crystals.