Ruta Meilutyte's title defence in the women's 100 metres breaststroke ended at the first hurdlethe Lithuanian failed to reach the semifinals of the World Championships in Doha on Monday.
Meilutyte, who took gold in the event at the 2012 London Olympics as a 15-year-old, was 17th quickest in the heats with a time of one minute and 7.79 seconds, more than three seconds off her gold medal swim in Fukuoka last July.
Meilutyte's setback followed Olympic champion Ahmed Fahnaoui's failure to make the men's 400m freestyle final on Sunday's opening day in a major shock.
World record holder Meilutyte will defend her 50m breaststroke title later in the meet.
China's Tang Qiantang is seeded top for the women's semis after swimming 1:06.16, three-tenths of a second quicker than Dutch second seed Tes Schouten at the Aspire Dome pool.
With title-holder Katie Ledecky skipping Doha, Italy's former world champion Simona Quadarella is in the box seat to win a second 1 500m gold.
The 2019 winner qualified fastest for the final with a time of 16:02.96 in her heat. Fukuoka bronze medallist Li Bingjie qualified third behind German second seed Isabel Gose.
German Lukas Maertens, who won a second 400m freestyle bronze on Sunday, topped qualifying for the men's 200m semifinals in a field missing Britain's defending champion Matt Richards and Fukuoka runner-up Tom Dean.
Claire Curzan, who agonisingly missed out on the United States' Fukuoka team after battling illness before the trials, was the fastest qualifier for the women's 100m backstroke semifinals (59.72 seconds).
South Africa's Pieter Coetze took top seed for the men's semifinals after swimming 53.32 in the heats.
World record holder and Olympic champion Adam Peaty will bid for the 100m breaststroke title in the evening session on Monday. American Kate Douglass is set to defend her 200m IM title in the final.