Here we show, for the ®rst time, thein vitro formation of ®lamentous aggregates of phosphorylated tau protein in SH-SY5Y human neuroblastoma cells. The formation of suchaberrant aggregates, similar to thoseoccurringinvivoin Alzheimer's disease and other tauopathies, requires okadaic acid, a phosphatase inhibitor, to increase the level of phos-phorylated tau, and hydroxynonenal, a product of oxidative stress that selectively adducts and modi®es phosphorylated tau.