Rookie Austin Cook finished his second round at eight-under 62 to put him in the lead after day two of the RSM Classic in Sea Island, with Padraig Harrington the only Irish golfer to make the cut.
Harrington had seven birdies in a second round 67 to finish the day four under par.
But Seamus Power had a poor start and a poor back nine and finished one below the cut line on two under. Graeme McDowell also missed out, on one under.
Cook started well as he produced eight birdies on the Seaside Course, including four in a row between holes 13 and 16.
A long-range birdie from 34 feet on the par-4 hole one and a six-foot putt for birdie on the par-4 ninth hole helped to power him into the top spot on 14 under.
The American sits just one shot ahead of his closest rival and fellow countryman Brian Gay, who shot six-under 64, while Chris Kirk, leader after day one of the event, slipped to joint third position with 70 on round two.
Scotsman Russell Knox also carded a second round of 70, putting him tied for 33rd on five under overall.
Meanwhile, former FedEx Cup champion Brandt Snedeker, playing for the first time since June after suffering a chest injury, pulled himself up the leader board to finish the round in joint sixth position.
He carded a five-under 67 on the Plantation Course, pouring in a 39-foot birdie putt on the par-4 6th hole, putting him six shots behind the pace.