Kauto Star and Long Run are set for a mouth-watering clash in the King George VI Chase at Kempton on Boxing Day.
The 11-year-old Kauto Star is aiming to win a record fifth title after he and stablemate Master Minded were confirmed by trainer Paul Nicholls on Tuesday.
Nicholls said: "I've had a chat with Clive [owner Clive Smith] and we're going to run Kauto and Master Minded."
Kauto defied the critics by beating Long Run to win the Betfair Chase at Haydock on 19 November.
Ruby Walsh will ride two-time Cheltenham Gold Cup winner Kauto Star, with Daryl Jacob aboard two-time Queen Mother Champion Chase winner Master Minded, who steps up to three miles for the first time.
Nicholls explained that the unpredictable lifespans of racing horses helped sway his and owner Smith's decisions.
"We saw with Tataniano and Denman recently how the smallest of injuries can end seasons and careers, and that brought into sharp focus that sometimes you have to seize the moment with racehorses," he said.
Amateur jockey Sam Waley-Cohen will take his usual seat onboard Long Run after avoiding a ban for taking the wrong course in a race at Fakenham on 12 December.
His 12-day suspension applies only on days of amateurs-only races, so it will not start until 1 January 2012.
Long Run won the weather-delayed King George in January 2011 and went on to clinch his first Cheltenham Gold Cup ahead of 2008 winner Denman and Kauto Star, the 2007 and 2009 victor, in March.
But Kauto Star defied the bookmakers and the retirement-mongers and beat his younger rival by eight lengths at Haydock last month to set up the prospect of a thriller at Kempton.
The other horses competing in the £180,000 showpiece include Henrietta Knight's Somersby, Philip Hobbs' Arkle winner Captain Chris, Diamond Harry, Nacarat and Golan Way.
RECENT KING GEORGE VI CHASE WINNERS
2010: Long Run
2009: Kauto Star
2008: Kauto Star
2007: Kauto Star
2006: Kauto Star
2005: Kicking King
2004: Kicking King
2003: Edredon Bleu
2002: Best Mate
2001: Florida Pearl
2000: First Gold