Analysis of the structures of the human amylase genes has demonstrated that this multigene family contains at least five tandem gene copies, closely related in sequence but with distinct tissue specific expression. The structures of the genes demonstrate that the human salivary amylase gene was derived from a preexisting pancreatic amylase gene. Insertion of a retrovirus upstream of the amylase gene is responsible for the alteration in tissue specificity. A parotid specific enhancer has been identified within the retrovirus by expression studies in transgenic mice. The independent origin of salivary amylase in rodents and primates suggests that there has been strong evolutionary selection for amylase in saliva. The amylase genes demonstrate a novel mechanism for evolution of new patterns of tissue specific gene expression.