Northern blotting analysis revealed different tissue distribution patterns of HMT mRNA between mice and rats. In the mouse, mRNA expression was detected in the brain, kidney and liver. In the rat, there was an extremely high mRNA signal only in the kidney. We isolated and characterized the rat and mouse histamine N-methyltransferase (HMT) genes from genomic DNA libraries. The rat HMT gene consists of 6 exons and 5 introns. The mouse HMT gene structure was similar to that of the rat, but had one additional exon 5' upstream from the exon containing a start codon, resulting in seven exons. Several long interspersed repetitive elements were located in the 5' flanking region of the rat and mouse HMT gene. Despite high sequence conservation of the regions around exon 6 and the 3' flanking region, the 5' flanking region had little similarity between the rat and mouse. Marked sequence similarities between rat and mouse introns were present near splice sites and outside the junction residues, suggesting the evolutionary relationship between the structural features of the rat and mouse HMT genes. This observation may explain the species difference of the tissue expression pattern of HMT mRNA.