Top-weight Minella Rocco has been declared a non-runner in the Randox Health Grand National at Aintree on Saturday on account of the ground.
Jonjo O'Neill's charge filled the runner-up spot in last year's Cheltenham Gold Cup and pulled out of this year's renewal on the morning of the race due to the prevailing testing conditions at Prestbury Park.
He was a best-priced 20-1 for the world's most famous steeplechase before being withdrawn on Friday morning.
Frank Berry, racing manager to owner JP McManus, said: "It's purely ground related, he's just not as good in soft-heavy ground.
"It's a real shame as he's been aimed at this for a long time, but there's no point him running on that ground."
Minella Rocco could be rerouted to the Coral Punchestown Gold Cup on April 25.
Berry added: "He's entered at Punchestown and I'd like to think he'd run there now, but the ground will have to start drying up soon.
"It's just not going to dry up in time for him (at Aintree), unfortunately."
Minella Rocco's defection means first reserve Thunder And Roses, who won the 2015 Irish Grand National, is guaranteed a run for trainer Mouse Morris.
Morris, who won the 2016 Grand National with Rule The World, will now fire a twin assault at this year's renewal, with Thunder And Roses, who will wear the number one saddle cloth, joining stablemate Alpha Des Obeaux.
He said: "If you're not in you can't win and it's good Thunder And Roses has got a run.
"The two horses have travelled over fine and everything is good. We can't complain."
The weights for all runners in the Grand National are now raised by 1lb. The new top-weight is Blaklion on 11st 10lb.