Untapable will not defend her crown in the Longines Breeders' Cup Distaff at Keeneland on Friday.
Steven Asmussen's four-year-old has spiked a temperature and will play no part in the Grade One feature.
Ron Winchell, of her owners Winchell Thoroughbreds, tweeted: "Untapable will not run in BC Distaff due to a slightly elevated temperature.
"Very disappointing after preparing all year for a repeat."
Illuminate, meanwhile, stretched out on the all-weather in the hands of Frankie Dettori ahead of the Breeders' Cup Juvenile Fillies Turf on Friday.
Connections of the young filly, trained by Richard Hannon, are wary about the prospect of more rain at Keeneland.
Hannon's assistant Tony Gorman said: "I didn't plan to work her but she was so fresh I had to.
"She has travelled well but the rain is a big worry.
"We didn't think we would get cut in the ground but it looks guaranteed we will."
Karakontie led the way on to the training track for the impressive French team that is hopeful of dominating the Breeders' Cup Mile on Saturday.
The four-year-old colt won the race 12 months ago and will be joined in the line-up by compatriots Make Believe, Impassable and Esoterique.
Karakontie is due to take up stallion duties at Gainsway Farm in Kentucky on Sunday and could be a final runner for Jonathan Pease, who is retiring from the training ranks.
