TUBULIN, the major component of microtubules, is a heterodimer of two chains, alpha and beta(1), both of relative molecular mass 50,000 (M(r) 50K) and sith 40-50% identity. The isotypic variety(2) and conformational flexibility of tubulin have so far made it impossible to obtain crystals for X-ray work(3). Structural knowledge of tubulin has been limited to about 20 Angstrom from X-ray diffraction of oriented microtubules(4), and from electron microscopy of microtubules and zinc-induced crystalline sheets in negative stain(5,6). The sheets consist of protofilaments similar to those in microtubules but associated in an antiparallel arrangement(7) and their two-dimensional character is ideal for high-resolution electron microscopy(8,9). Here we present a three-dimensional reconstruction of tubulin to 6.5 Angstrom resolution, obtained by electron crystallography of zinc-induced two-dimensional crystals of the protein, The alpha- and beta-subunits appear topologically similar, in agreement with their sequence homology(10). Several features can be defined in terms of secondary structure. An apparent alpha-helical portion, adjacent to both interdimer and inter-protofilament contacts, is tentatively attributed to a segment near the carboxy terminus of the protein. We can assign the alpha- and beta-subunits on the basis of projection studies of the binding of taxol*, which show one taxol site per tubulin heterodimer, in agreement with the known stoichiometry of taxol in microtubules(11). These studies indicate that taxol affects the interaction between protofilaments; to our knowledge, this is the first time that a ligand-binding site has been visualized in the tubulin molecule.