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World record-holder and reigning world and Olympic champion Ledecky, who placed sixth in the 100 free, took the 800 crown in 8mins 11.50secs with Leah Smith, sixth at Rio, taking second, 8.96 seconds back.
Ledecky could swim in four individual events and two relays at next month's World Championships in Budapest, Hungary, with a strong showing at this five-day meet in Indianapolis, Indiana.
"It's important to get the job done here and get to Budapest and do a lot," Ledecky said. "So far I'm setting myself up well but it's just the first day."
While it was a 2017 world best, the winning time was only the ninth-best for Ledecky, who captured 200, 400 and 800 free Olympic gold last year in Rio - defending the 800 crown she won in London - and helped the US women's 4x200 relay win as well.
Ledecky won the world 400, 800 and 1,500 freestyle titles and shared in a 4x200 free relay win in 2013 in Barcelona then defended those crowns and adding the 200 world title in 2015 at Russia.
Mallory Comerford, who matched Ledecky for the 200-yard free US college crown, won the women's 100 free in 52.81 seconds, shaving 1.1 seconds off her pre-meet personal best.
Rio Olympic co-champion Simone Manuel was second in 53.05.
Ledecky was sixth in 54.35, matching her seed position. That, combined with the second-best US split time on the Rio 4x100 free relay, should make her a contender to swim the same relay at Budapest.
"All of us want to throw down some good times," Ledecky said. "We want to keep that momentum going from 2016."
Ledecky will swim for world berths and US crowns Wednesday in the 200 free, Friday in the 400 free and Saturday in the 1,500 free.
Nathan Adrian, a five-time Olympic and world champion on relays, out-touched Caeleb Dressel at the wall to win his eighth US title in the men's 100 freestyle in 47.96, edging double Rio relay gold medalist Dressel by .01.
Jack Conger, who helped the US 4x200 freestyle relay win Rio Olympic gold, captured the men's 200 butterfly in 1:54.47, beating Pace Clark by .11 of a second. Top seed Chase Kalisz, who took Rio 400 individual medley silver, was third in 1:54.79.
Hali Flickinger, who finished seventh at last year's Rio Olympics, claimed her second women's 200 butterfly national crown in 2:07.60, beating Dakota Luther by 1.11 seconds.
True Sweetser, the 2015 US runner-up, won the men's 1,500 free in 14:59.73 with Robert Finke in second, 1.58 seconds back.
71% of retail investors in the UAE hold stocks in companies engaged with AI
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