The microtubule-binding protein tau is important in establishing and maintaining neuronal morphology and is a major component of the neurofibrillary tangles (NFTs) characteristic of Alzheimer's brain. The neuron-specific tau transcript undergoes complex alternative splicing. The human tau gene has been cloned and mapped. The restriction analysis and partial sequencing of the gene shows that it contains (1) four alternatively spliced exons previously described in rodent and bovine but not in human tau cDNAs and (2) two CpG islands, one associated with the promoter region, the other with exon 9. Examination of human tau mRNA indicates that the human cerebrocortical splicing pattern differs from that previously reported for the murine and bovine tau mRNAs, despite conserved exon organization in all three genes.