In a major shift in electoral strategy, the U.S. Chamber of Commerce plans to launch an aggressive, $40 million campaign to defeat state and federal candidates who oppose their pro-industry agenda, starting with Senate Minority Leader Tom Daschle (D-S.D.).

Bill Miller, the head of the chamber’s political arm, charged that Daschle has “on occasion been supportive of the business community, but for the most part, he has been more of an obstacle than an ally.”

Miller said Daschle’s Republican opponent, former Rep. John Thune (S.D.), is a “great friend of the business community and we will do everything we can to be supportive of him.”

Dan Pfeiffer, a spokesman for Daschle, said Democrats hope to turn the chamber’s endorsement of Thune against him.

“Tom Daschle has taken on special interests for years, so we are not shocked when they target him for defeat,” Pfeiffer said.

Still, the chamber’s bold campaign against the top Democrat in the Senate reflects a quiet and important change in tactics for the nation’s largest business lobby.

Until recently, the Chamber of Commerce was reluctant to get drawn into close political contests involving incumbents like Daschle whom the business group might need down the road.

“There was always a frustration that they were the first ones at the door when they wanted a bill, but when it comes election time, they are nowhere to be found,” said one former Republican operative.

But in the past few years, the chamber has launched a well-organized effort to install business-friendly candidates to state Supreme Courts and attorney general offices.

Now the chamber plans to become a bigger player in House and Senate elections.

“The chamber used to be a broken-down Buick: They put out press releases and communicated with their members,” said another Republican campaign official. “Now they are entering the 21st century with real voter contact and a commitment to moving votes.”

The chamber’s decision to support Thune over Daschle is symbolic of the new approach to election-year politics.

According to the strategists with the business lobby, the chamber plans to use mail, phone and perhaps even television and radio spots to cast Daschle as an opponent of the business community.

The campaign will be run by Miller, along with GOP campaign veterans Stan Anderson and Scott Reed, and funded by contributions from the chamber’s 3 million business members.

Though the strategists behind the chamber’s campaign hope to defeat Daschle, they also hope to divert Democratic resources from other important races.

“It will have a big ripple effect,” said one Republican involved in the business campaign. “It will take a lot of national Democratic resources away from other states.”

The recently enacted campaign finance law may give outside groups like the Chamber of Commerce more of an ability to influence Congressional elections because the national political parties don’t have as much money to fund large advertising and get-out-the-vote campaigns.

“An opportunity exists to be a larger voice than in previous elections,” Miller said.

Established entities like the chamber could also be buttressed by a Federal Election Commission proposal last week that could ban so-called 527 organizations from funding media campaigns for Congressional candidates.

“Any time the 527 groups are weakened, our position is strengthened,” Miller said. “We are still going to be able to communicate.”

Daschle is not the only Democrat that the chamber has decided to target.

At a meeting last month, Chamber President Tom Donahue and the members of the board settled on a number of states and districts where the chamber will target its advertising and get-out-the-vote efforts.

Aside from Daschle, the chamber hopes to help Rep. George Nethercutt (R-Wash.) defeat Sen. Patty Murray (D), while ensuring that Sen. Lisa Murkowski (R-Alaska) is elected to another term against former Gov. Tony Knowles (D).

The chamber also will be active in open-seat races in North Carolina, South Carolina, Georgia and Florida.

On the House side, few targets have been selected because many Republican and Democratic challengers have yet to emerge.

However, the chamber plans to support the GOP candidates in the two open seats in Pennsylvania, as well as vulnerable Republicans Steve Pearce in New Mexico, Rick Renzi in Arizona and Jim Matheson in Utah.

To be sure, not all of the chamber’s targets are Republicans: The business group has decided to endorse Sen. Blanche Lincoln (D-Ark.).

“She has been a very strong friend of ours,” Miller said.