Champion hurdler Faugheen has a leg injury and will miss the defence of his Champion Hurdle title at Cheltenham, his trainer Willie Mullins says.
The eight-year-old, who beat Arctic Fire and Hurricane Fly in last year's race, will be out until next year.
Jockey Ruby Walsh described his absence from the race on 15 March as "like whipping the ace out of the pack".
Faugheen's injury means another Mullins runner, Annie Power, may now be aimed at the Champion Hurdle.
The Irish trainer, who trained all of last year's top three finishers, also has Arctic Fire and Nichols Canyon entered for this year's race.
Mullins said: "We think the prognosis [for Faugheen] is very good and he should be back as good as new next year."
BBC Sport horse racing correspondent Cornelius Lysaght:
"You don't have to have backed Faugheen to as short as 4-1 ON favourite to repeat his 2015 success to be disappointed. Beaten only once in 13 starts, he's one of jump racing's biggest stars, whose appearance at Cheltenham was much anticipated.
"There's no reason at all why he shouldn't make a complete recovery. The intriguing possibility now is that another big Willie Mullins name, Annie Power, could be switched to the Champion Hurdle for which she'd have to be added as a late entry for £20,000."