Ruby Walsh will not ride in Saturday's Grand National feature race after suffering a hairline fracture of the wrist.
The Irishman had been set to be on the former Cheltenham Gold Cup runner-up Sir Des Champs, trained by Willie Mullins, but has been forced to sit out.
He sustained the injury after falling with another of Mullins' horses, Vautour, in the Melling Chase on Friday, and then again with Blood Cotil in the Topham.
Walsh had been expected to recover, despite failing to mount either Bellshill or Battleford later in the day, with Mullins explaining that the 36-year-old had stood himself down and would be fine for Saturday.
But the trainer later confirmed Walsh's withdrawal.
Injury has previously ruled the rider out of both the 2010 and the 2012 Grand Nationals.
Nina Carberry will replace Walsh on Sir Des Champs, while Paul Townend comes in for his other engagements, Yorkhill and Douvan.