The restriction landmark genomic scanning (RLGS) method is a high-spee
d genome scanning system which is based on the concept that restrictio
n enzyme sites can be used as landmarks throughout the genome. It empl
oys direct end-labeling of the genomic DNA digested with a rare-cuttin
g restriction enzyme, followed by high-resolutional two-dimensional el
ectrophoresis. Recently, this system was further developed to lower co
st and to simplify the procedure. This paper reviews the RLGS principl
e and the breakthroughs enabling its further development. Also present
ed is the precise protocol of the newest version (RLGS Ver. 1.8) that
offers cost effectiveness and an expanded production system. Finally,
the advantages of this new RLGS method and prospects for its widesprea
d application are discussed.