The crystallization and structure determination of recombinant human apolipoprotein A-I (apo A-I), the major protein component of high-density lipoprotein, is described. The fragment crystallized, residues 44-243 of native apo A-I [apo Δ(1-43)A-I], is very similar to intact native apo A-I in its ability to bind lipid, to be incorporated into high-density lipoproteins and to activate lecithin - cholesterol acyl transferase. Apo Δ(I-43)A-I crystallizes from 1.0-1.4 M sodium citrate pH 6.5-7.5 in space group P212121, with unit-cell parameters a = 97.47, b = 113.87, c = 196.19 Å (crystal form I). The crystals exhibit unusual diffraction intensity spikes and axial extinctions that are discussed in the context of the 4 Å, crystal structure. When flash-cooled to 100 K, the crystals diffract synchrotron radiation to 3 Å, resolution. Radiation sensitivity and crystal-to-crystal variation have hindered the assembly of a complete 3 Å data set.