Paired helical filaments isolated from the brains of patients with Alzheimer's disease are composed of a major protein component, the microtubule-associated protein termed tau, together with other nonprotein components, including heparan, a glycosaminoglycan, the more extensively sulfated form of which is heparin. As some of these nonprotein components may modulate the assembly of tau into filamentous structures, we have analyzed the ability of the whole tau protein or some of its fragments to self-assemble in the presence of heparin. Different tau fragments, all of them containing some sequences of the tubulin-binding motif, can assemble in vitro into filaments. We have also found formation of polymers with the 18-residue-long peptide corresponding to the third tubulin-binding motif of tau. This suggests that the ability of tau for self-assembly could be localized in a short sequence of amino acids present in the tubulin-binding repeats of the tau molecule.