Democratic Sen. Ben Nelson is stepping down after nearly two decades.
It's a move that opens the door for Republicans to pick up another Senate seat.
The 70-year-old conservative Democrat made the announcement Tuesday, saying he was ready to "step away from elective office, spend more time with my family, and look for new ways to serve our state and nation."
Nelson is the only Democrat in Nebraska's five-member congressional delegation.
Right now, no other Democrat is in line to take his place in the conservative state.
Sen. Jim Webb, D-Va., and Sen. Kent Conrad, D-ND, are among several other Democrats stepping down this year.
Republicans need to gain just four seats to reclaim control of the Senate.
Democrats acknowledged they will face a tough fight to hold on to Nelson's seat, but they said a crowded GOP primary field with no obvious front-runner could help.
"This virtually guarantees a Republican victory in 2012," said University of Nebraska Lincoln political scientist Mike Wagner. "There's almost no scenario in which a Democrat can win -- especially at this late stage."