The heterotetrameric adaptor proteins (AP complexes) link the outer lattice of clathrin-coated vesicles with membrane-anchored cargo molecules. We report the crystal structure of the core of the AP-1 complex, which functions in the trans-Golgi network (TGN). Packing of complexes in the crystal generates an exceptionally long (1,135-Å) unit-cell axis, but the 6-fold noncrystallographic redundancy yields an excellent map at 4-Å resolution. The AP-1 core comprises N-terminal fragments of the two large chains, 1 and ␥, and the intact medium and small chains, 1 and 1. Its molecular architecture closely resembles that of the core of AP-2, the plasmamembrane-specific adaptor, for which a structure has been determined. Both structures represent an ''inactive'' conformation with respect to binding of cargo with a tyrosine-based sorting signal. TGN localization of AP-1 depends on the small GTPase, Arf1, and the phosphoinositide, PI-4-P. We show that directed mutations of residues at a particular corner of the ␥ chain prevent recruitment to the TGN in cells and diminish PI-4-P-dependent, but not Arf1-dependent, liposome binding in vitro.