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.
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.
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 Ireland's 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 Irish raiders.
Coney Island was sidelined for almost a year after splitting Our Duke and Disko in the Neville Hotels Novice Chase at Leopardstown, but made an impressive return in a graduation chase at Ascot last month.
Harty has also given his charge an entry in the Ryanair Chase at Cheltenham and his Festival target is likely to become clear after his next run, at either Ascot or Leopardstown in February.
The trainer said: "I was delighted with Coney Island at Ascot. He has come out of it fit and well, and is ready to go again.
"He has been entered for the Timico Cheltenham Gold Cup and the Ryanair Chase, and will also have entries in the Irish Gold Cup on February 4 and the Ascot Chase a fortnight later.
"We will go for one of those two and then make a decision about which race to aim for at Cheltenham after that."
He went on: "I think the Gold Cup picture looks as much as it did before Christmas. Might Bite did nothing wrong, Sizing John did, but that might have been down to the proximity of his prep race, and nothing else really came to the fore.
"My fella has shortened up in the betting after Ascot, but it was only a graduation chase. Touch wood and all being well, we will be able to decide where we are going after his prep run.
"I don't have any concerns about his stamina, but it would have been stupid not to put him in the Gold Cup and the Ryanair as we are still nine weeks out from Cheltenham and can finalise plans nearer the time."