Previous studies have shown that the levels of the microtubule-associated protein tau in the CSF of patients with Alzheimer's disease (AD) are elevated compared with age-matched controls. In spite of these findings, the nature of tau in CSF has not been well documented. In the present study, tau was immunoprecipitated from CSF of patients with AD or acute stroke, as well as normal elderly controls, followed by immunoblot analysis. In all cases, CSF tau consisted primarily of a band migrating at 26-28 kDa. In AD and stroke patients, several smaller tau fragments were also detected. No intact tau was detected in any of the CSF samples examined. Further immunoprecipitation studies showed that the majority of the tau fragments contained the amino terminus of the molecule. Treatment of CSF tau with alkaline phosphatase did not alter the electrophoretic properties of the fragments. These studies clearly demonstrate that CSF tau is truncated rather than intact.