The crystallization of recombinant human apolipoprotein A-I (apo A-I), the major protein component of high-density lipoprotein, in a new crystal form 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(1-43)A-I crystallizes, in the presence of β-D-octylglucopyranoside, in space group I222 or I212121, with unit-cell parameters a = 37.11, b = 123.62, c = 164.65 Å and a diffraction limit of 3.2 Å. These form II crystals grow under conditions of significantly lower ionic strength than the original form I crystals (space group P212121, a = 97.47, b = 113.87, c = 196.19 Å, diffraction limit 3.0 Å). Packing arguments show that the unusual open conformation of apo Δ(1-43)A-I found in the form I crystals cannot be packed into the smaller oddly proportioned form II unit cell. Monomeric apo Δ(1-43)A-I, as either a four-helix bundle (~75 x 30 x 30 Å) or an extended helical rod (~150 x 20 x 20 Å), can be packed into the form II unit cell. It is concluded, therefore, that apo Δ(1-43)A-I may have crystallized in one of these distinct conformations in the form II crystals.