Tau in cerebrospinal fluid (CSF) has been proposed as a diagnostic marker for Alzheimer's disease (AD). This paper presents a new sensitive sandwich ELISA allowing quantitation of tau from 8 microl CSF/well. A human specific monoclonal tau antibody HT7 was used as a capture antibody and a mixture of polyclonal tau antibodies, 92e and R134d was used as reporter antibodies. Tyramide signal amplification (TSA) technology was used in the last step to increase the sensitivity. With this TSA-ELISA, the lowest detection limit for tau was 14.3 pg/ml. Tau levels in CSF were found to be increased in AD patients (807+/-304 pg/ml, p<0.001) compared with controls (252+/-94 pg/ml). Thirty-five of 38 AD cases (92% sensitivity) yielded signals greater than cutoff, while only 1 of 38 control cases (97% specificity) was greater. A highly significant correlation was found between this assay and a commonly used kit, INNOTEST hTAU Antigen.