Gavin McDonnell's dream of joining twin brother Jamie as a world champion was shattered as classy Mexican Rey Vargas scored a points decision to land the vacant WBC super-bantamweight title.
The 30-year-old produced a display of immense grit - landing telling blows in the ninth round - but his 26-year-old opponent's confident work throughout saw him gain a 114-114 117-111 116-112 decision.
Victory would have delivered Britain's first simultaneous twin world champions, with Jamie McDonnell already in possession of the WBA bantamweight belt.
But Vargas - unbeaten in 29 bouts - was rewarded for his control of the early exchanges and left the noisy Ice Arena in Hull with his first world title.
Vargas, with Iganacio Beristain - who has trained Oscar de la Hoya and Juan Manuel Marquez to world titles - in his corner, took the middle of the ring early and confidently landed three-shot combinations with McDonnell visibly cautious against a man with 22 previous knockouts.
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In the build-up to the fight, McDonnell's promoter Eddie Hearn said he pushed for the bout to take place at the "down and dirty" Hull Ice Arena in the hope the "bear-pit" atmosphere could do "strange things" to the travelling fighter.
There were moments of home hope, as McDonnell landed a stinging right in the 10th but in just his third fight outside Mexico, Vargas even had the temerity to smile back at his man after taking some punishment late on.
The younger man's confidence to switch from making the fight to boxing on the back foot near the ropes perhaps showed he knew he had built a good early lead. McDonnell's head movement was energetic throughout, while his opponent was happy to remain static at times as he waited to pick his attacks.
Now 19 fights into his career, McDonnell can take great pride from the heart he showed and none of the 3,500 in the venue appeared to feel short-changed by his efforts.
In truth, he simply came up against a fighter who carried plenty of power in his 8st 10lb frame, and showed variation and a cool head to handle the occasion.
At the final bell, Vargas threw his hands into the air before slumping to the ropes and looking to the heavens. McDonnell in contrast seemed to know hopes of family history were over, for now.
Earlier in the night, London 2012 Olympic champion Luke Campbell maintained his momentum as he seeks a world title shot in 2017 - "the biggest year of my career", according to the Hull fighter.
The 29-year-old lightweight recorded his fourth straight win following a shock defeat in 2015 to Yvan Mendy, with a series of crushing left hands to Jairo Lopez.
The Mexican, down in the first, somehow made the second round but was flattened by a left uppercut. Campbell, who began training in Miami after the Mendy defeat, showed his typically energetic style and now has hopes of a shot at WBC champion Mikey Garcia.
Another Hull fighter, Tommy Coyle - beaten by Campbell in 2015 - kept his hopes of a return to world level alive with a third-round stoppage of Rakeem Noble.
'I lost by three rounds' - what they said
Gavin McDonnell, talking to BBC Radio 5 live, said: "I will learn, I know where I went wrong, I am disappointed, but I will work so hard.
"I had him winning by a couple of rounds, probably three rounds in my opinion. Everyone is in with a puncher's chance - if I can improve my speed and power I will land and I can beat that kid.
"If we do have a rematch, I know how to beat him in the future."
In an interview with Sky Sports, he added: "I gave it everything and I hope everyone enjoyed it. I feel like I let everyone down.
"I just fell short at the end. I felt all right in there, I was a bit too eager and I couldn't get close enough. I will come again - I have only had 18 fights and I want to show I belong at this level.
"I have no doubt I will be a world champion."
Promoter Eddie Hearn told BBC Radio 5 live: "I think Gavin started too slowly and he was always chasing it. Vargas was very good - he had excellent feet and confidence.
"To put in a performance like that, Gavin should be very proud but ultimately he was not good enough. I think Rey Vargas will go on to do a lot in the sport.
"Gavin has improved so much but he was not letting his hands go and that was the frustrating thing. It was a little bit of inexperience. If he did what he did in the ninth from the fifth round onwards then he would've had a chance."