The biogenic amine histamine is an important modulator of numerous physiologic processes, including neurotransmission, gastric acid secretion, and smooth muscle tone. The biosynthesis of histamine from histidine is catalyzed by the enzyme L-histidine decarboxylase (HDC). This homodimeric enzyme is a pyridoxal phosphate (PLP)-dependent decarboxylase and is highly specific for its histidine substrate. A high degree of homology was found among the HDCs and the dopa decarboxylases (DDC) of rat, mouse, and human.The gene contains 12 exons spanning approximately 24 kb. Genomic DNA blot analysis suggested that HDC is encoded by a single copy gene. Structural analysis showed that the observed heterogeneity of the HDC mRNA is caused by alternative splicing.