The FBI is investigating 14 companies embroiled in the sub-prime mortgage crisis as part of a crackdown on improper lending.
It did not identify the companies but said the investigation encompassed developers, sub-prime lenders and investment banks.
FBI officials said the agency was looking at instances of accounting fraud and insider trading.
The cases could lead to potential civil or criminal charges, the FBI said.
The FBI said it viewed mortgage fraud as an increasing threat to the national economy.
It said that there had been 1,200 cases of mortgage fraud for the 2007 financial year compared with just 400 in 2006.
The crisis in the sub-prime lending market has hit financial markets worldwide.
The FBI said it was investigating the cases with the US market regulator, the Securities and Exchange Commission.
The SEC has opened about three dozen investigations into the collapse of the sub-prime market.
Targets of the SEC probe include Swiss bank UBS and US banks Morgan Stanley, Merrill Lynch and Bear Stearns, Reuters news agency reported.
It was not clear whether any of these firms were involved in the FBI investigation.
The sub-prime market is focused on providing home loans to those with poor or limited credit histories.
Many of these borrowers have been unable to keep up with payments and face losing their homes.
The wider crisis emerged as many of these mortgages were converted into financial instruments and sold on to investors including the big investment banks.
Defaults on these loans caused a steep drop in the value of related investments and has led to more than $100bn of losses at banks worldwide.