The U.S. Chamber of Commerce -- already a major force in fighting the Obama administration's big-ticket domestic agenda items -- is set to play an out-sized role in this fall's midterms.

The group will target vulnerable Democrats in up to two dozen states with ads, get-out-the-vote operations and other grass-roots efforts. The chamber plans to spend at least $50 million on political races and related activities this year, a 40 percent increase from 2008