Tau messenger RNA in situ hybridization in human postmortem brain revealed that neurons are the predominant cell type labeled. The probe used includes the nucleotide sequence coding for the amino acids recognized by the well-characterized tau monoclonal antibodies 5E2 and tau 1. The distribution of the tau RNA is abundant throughout the neuronal somata and into the proximal parts of dendrites of pyramidal cells in the cerebral cortex and the hippocampus. The distal extent to which silver grains could be visualized in the pyramidal cell dendrite was comparable to that seen with a probe to ribosomal RNA. In contrast to the tau probe the ribosomal probe also labeled glial cells. Sections hybridized with the tau probe and then double-labeled with thioflavine S revealed that neurons containing neurofibrillary tangles continue to synthesize tau protein.