The structure of the protein tumour necrosis factor (TNF) was determined from crystals of space group P3(1)21 which contain six copies of the TNF monomer per crystallographic asymmetric unit [Jones, Stuart & Walker (1989). Nature (London), 338, 225-228]. The nature of these crystals (relatively high crystallographic symmetry coupled with multiple copies of the protein in the asymmetric unit) led to some peculiarly challenging problems at several points in the structure determination. In particular, (1) self-rotation function calculations failed to yield clearly interpretable solutions, (2) the analysis of difference Patterson maps for heavy-atom derivatives required the development of a Patterson search program suite GROPAT. The redundancy in the asymmetric unit allowed refinement of poor-quality isomorphous phases at 4 A resolution and phase extension from 4 to 2.9 A resolution using real-space symmetry averaging and solvent flattening in the absence of any isomorphous phase information. Despite further difficulties caused by structural differences between the six independent copies of the monomer the resultant electron density map was of high quality and proved to be easily interpretable.