During World War II, the nation began a top-secret project to build the first atomic bomb. The Army created the Manhattan Engineering District (MED) to carry out much of the work of the so-called "Manhattan Project" during World War II. After the war, the nation sought ways to use nuclear energy for peaceful purposes and formed the Atomic Energy Commission (AEC) in 1946. Some of this work was performed in the St. Louis area.

From 1942 to 1957, the MED/AEC contracted with Destrehan Street Refinery and Metal Plant (later Mallinckrodt Chemical Works) to process natural uranium, producing uranium oxide, trioxide and metal uranium. This became the St. Louis Downtown Site (SLDS).

In 1946, MED acquired the St. Louis Airport Site (SLAPS), a 21-acre site just north of the St. Louis Airport for storage of residues and other material from the downtown site. In subsequent years, adjacent properties became contaminated as a result of erosion.

In 1966, a private company purchased SLAPS residues, which contained valuable metals, and began hauling them to a site on Latty Avenue in Berkeley, Missouri, after which they were sold for their commercial value. Later, the material was sold again and much of it shipped to Colorado. Surveys in 1977 showed that the former owners had left contamination on the Latty Avenue property. Part of this site was latter called the Hazelwood Interim Storage Site (HISS).

In addition, transport and migration of the material spread contamination along the haul routes to nearby Vicinity Properties. Although the federal government was not responsible for this contamination, Congress directed that the government add these sites to the Formerly Utilized Sites Remedial Action Program (FUSRAP).

On October 4, 1989, SLAPS and HISS were added to the Environmental Protection Agency's National Priorities List (NPL).