Little information is available concerning the genetics of Helicobacter pylori. This chapter discusses the genome sizes of different H. pylori isolates and to construct a physical map of the chromosome from one H. pylori strain. Chromosomal DNA from H. pylori strain UA763 was digested with 25 different restriction endonucleases to identify those suitable for mapping the genome. The size of the H. pylori genome is consistent with the requirement of this organism for a complex growth medium, its failure to ferment carbohydrates or degrade many complex substances, and its general biochemical inertness. Several groups of workers have analyzed H. pylori DNA using chromosomal restriction endonuclease digestion with enzymes that have frequent cut sites and have separated the DNA fragments by conventional agarose gel electrophoresis. The genome size of H. pylori strains, which ranged from 1.6 to 1.73 Mb, was fairly similar to those of Campylobacter jejuni and Campylobacter coli.