Murray admitted he did struggle with the midday heat
Andy Murray battled hard but succumbed to American Mardy Fish 6-7 (7-9) 6-1 7-6 (7-5) in intense heat in the last eight of the Cincinnati Masters.
While not at his best, world number four Murray showed resilience to take the first set on a tie-break.
The Scot was treated court-side for the heat in the second set, which Fish took with ease as Murray's strength waned.
Murray showed immense reserve to force the final set to a tie-break but Fish proved just too strong for the Scot.
World number 36 Fish will now face close friend Andy Roddick in the semi-finals after he beat Novak Djokovic 6-4 7-5.
Roger Federer is also into the last four after a 6-4 7-5 win over Nikolay Davydenko of Russia, but Rafael Nadal suffered a surprise 6-4 4-6 6-4 by Marcos Baghdatis.
Nadal committed 30 unforced errors in the first two sets and double-faulted on break point in the ninth game, but said: "The matches are a lot of points, but just a few points are the key of the match.
Physically (this week) will have been very good for me before the US Open
"I think I did the more difficult thing and that is change the dynamic of the match because I wasn't playing well."
Murray's defeat ends a seven-match unbeaten run which includes his success at the Rogers Cup in Toronto last week.
The players took to the court at 12pm local time (1700 BST) in temperatures reaching 33 degrees in the shade, after Murray's request for a later start on Friday was rejected by tournament officials.
The world number four had struggled with rising temperatures in Ohio during his three-set victory over Latvia's Ernests Gulbis on Thursday.
"If you ask for a late match and you're put on first, that's not...that's pretty....," said Murray, hesitating to pick his words carefully.
"I don't ever request really when to play. I don't make many demands at all during the tournaments."
Murray revealed that his request was rejected because organisers said opponent Fish was playing doubles later in the day.
"I'm not sure, the way the tennis works, I don't think matches should be scheduled around the doubles because it's the singles that's on the TV," he added.
While not at his fluid best, especially on serve, Murray managed to hold on during a hard-fought first set.
Neither player could pierce the other's serve, with the Scot prevailing in an equally tight tie-break.
However, the complexion of the match shifted when Murray took a bathroom break early in the second.
The cool, air-conditioned indoor surroundings had a catastrophic effect on Murray's well-being, complaining of dizziness after losing his serve in the first and third games.
He was administered a cold towel around his shoulders, along with ice packs under his arm, to bring his body temperature down, but his game deteriorated during that period as Fish seized control of the match with some strong forehand hitting and powerful serving.
Murray said he had considered withdrawing from the match at one point but decided to try to grind out a victory.
"You always try and finish matches. I think I've pulled out of maybe one match, two matches out of over 300 or something on the tour," he added.
"It does cross your mind a little bit when you're kind of struggling like that. But the doctor and the physio did a good job with the ice and cooling me down a little bit."
Murray's exhausted demeanour between points belied the depths of his resilience and he rallied to once again prove highly competitive in the third set - hanging in to force a decisive tie-break.
But Fish was just able to come out on top in a see-saw finale to bring to an end Murray's unbeaten run in a match that lasted just short of three hours.
Murray now has 10 days to prepare for the fourth and final Grand Slam of the year, the US Open, which begins on 30 August.
"Physically (this week) will have been very good for me before the US Open," said Murray, who reached the final at Flushing Meadows in 2008.
"I'm going to be fresh when I get there, but I've played three long matches, two to 7-6 in the third, and another three-setter in the first round was definitely beneficial.
"I just would have liked to have been given a better opportunity to recover."
Roddick's impressive 6-4 7-5 win over Djokovic showed he is over the bout of glandular fever which has held him back and seen him lose form in recent months.
"Once you decide you are playing you forfeit any excuses," he said, when asked about his health.
One of those recent defeats was to Fish, at last month's ATP Classic in Atlanta, which ended a run of nine straight wins for Roddick over his friend.
"We know each other probably better than any other two guys on the tour," said Roddick. "There won't be many secrets, that's for sure."