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The 72-year-old Kiffin, who came to USC when his son, Lane, was hired as coach in January 2010, said in a statement he plans to pursue opportunities in the NFL. He said he made his resignation announcement now to help USC's recruiting efforts and to keep attention on the team's bowl-game preparation.
"I really enjoyed my time at USC and the opportunity I had to work with our players and coaches," Monte Kiffin said in the statement, released Thursday night on the school's official site. "The chance to work for my son, Lane, was unique and memorable, but we always treated each other professionally on a coach-to-coach basis."
With most of USC's coaches out on recruiting trips during an off week for the team, players had not officially been informed of the news as of 11 p.m. ET Thursday.
USC (7-5, 5-4 Pac-12) started the season as the AP's preseason No. 1 team but fell out of the rankings entirely after losing three games in November, and four out of the final five. The Trojans are the first team in 48 years to complete such a drop, and Monte Kiffin and his defense absorbed much of the blame.
The Trojans lost back-to-back games to Arizona and Oregon despite scoring a combined 87 points, with Kiffin's defense allowing a school-record 62 points and 730 yards to the Ducks.
His conservative style of defense, developed in the NFL, worked well against pro-style offenses at the college level but struggled to stop the spread. Kiffin has been credited as the inventor of the "Tampa-2" zone defense, but he veered away from that style at USC after the Trojans struggled on defense in 2010.
Kiffin's official title with the Trojans was assistant head coach, but he called USC's in-game defensive schemes and led defensive meetings. Ed Orgeron is the Trojans' defensive line coach and holds the defensive coordinator title.
Orgeron is a candidate to take over the role of defensive play-caller. Other potential candidates could include San Diego Chargers linebacker coach Joe Barry, who coached USC's linebackers from 2010-11 and has been an NFL coordinator in the past.
Lane Kiffin said in a statement Thursday that he plans to begin a search for a new coach immediately. It's unclear if the new coach would take over play-calling duties.
"I respect my father's decision and his desire to return to the NFL," Lane Kiffin said in a statement. "We are very appreciative of the hard work and effort that he put in at USC these past three years. He has a tremendous passion for coaching young men and he is a phenomenal recruiter. "The timing of this allows us to move forward now in the hiring of a new coach."
Before USC, the Kiffins had worked together for one season, in 2009 at Tennessee, where Orgeron also worked.
Monte Kiffin's reported $1.5 million salary at USC was a significant sum for a college assistant. He was making as much as Arizona head coach Rich Rodriguez and more than twice as much as Colorado head coach Jon Embree, who was fired earlier this week.For that amount, USC could give many NFL defensive coordinators and college head coaches a raise. Kiffin has been a football coach for 47 years, including 26 in the NFL, where he won a Super Bowl with the Tampa Bay Buccaneers in 2003. He hasn't sat out a season of football without coaching since the mid-1960s. He said Thursday that he expects his son's program to rebound soon. "Although things didn't always go as well as we would have liked this year from a defensive and win-loss standpoint, I will leave USC with the utmost respect for the University, the Trojan Family and, most importantly, the players I had the good fortune to coach," Monte Kiffin said in a statement. "I see great things ahead for the USC football program." ESPNLosAngeles.com's Arash Markazi contributed to this report.