Last year's winner Sizing John and ante-post favourite Might Bite feature among 38 entries for the Timico Cheltenham Gold Cup.
Jessica Harrington's Sizing John was an impressive winner of the blue riband event last March and made a spectacular seasonal reappearance in the John Durkan Memorial Punchestown Chase last month.
However, he is a general 6-1 shot to successfully defend his crown at Prestbury Park after a disappointing showing in the Christmas Chase at Leopardstown over the festive period.
An 18-strong Irish contingent includes multiple Gold Cup runner-up Djakadam, who is one of five entries for Willie Mullins as he bids to win the race for the first time. Ladbrokes Trophy winner Total Recall is another potential challenger for the perennial champion trainer.
Noel Meade's Christmas Chase winner Road To Respect, his high-class stablemate Disko, Harrington's Irish Grand National winner Our Duke and the Eddie Harty-trained Coney Island are other possible raiders from across the Irish Sea.
Might Bite is the 7-2 market-leader to provide Nicky Henderson with his third Gold Cup triumph following the previous victories of Long Run in 2011 and Bobs Worth in 2013.
The nine-year-old was a remarkable winner of the RSA Chase at last year's Festival after almost throwing the race away on the run-in and was last seen winning the King George VI Chase on St Stephen's Day.
Mark Bradstock's 2015 Gold Cup hero Coneygree is in mix once more, while Colin Tizzard could call upon Native River, who has not been seen since finishing third in last year's renewal, and the popular veteran Cue Card.
Other hopefuls for the home team include the Nigel Twiston-Davies-trained pair of Bristol De Mai and Blaklion and last year's runner up Minella Rocco, trained by Jonjo O'Neill.