A powerful method for localizing the genes responsible for genetic diseases is to "mark" each chromosomal region so as to permit its inheritance to be tracked in families carrying the disease; the disease gene must lie in the same region as any marker with which it is co-inherited. Chromosomes can be efficiently marked in this way by using restriction fragment length polymorphisms (RFLPs). We describe the construction of a map of the human genome with over 550 RFLP markers, such that over 95% of the genome is detectably linked to one or more of these markers. This map will make possible efficient searches for genes underlying a variety of disorders, both simple and complex, and lead to the development of presymptomatic diagnostic tests for these diseases.