United States's women
clinched the 4x100m medley relay gold
for the first time since Sydney 2000 with a new world record time of 3:52:05.
Great Britain, who qualified fifth from their heat, could only managed eighth.
The fastest of the qualifiers, Australia, winners of the event in 2008 and 2004, could only manage second and were pushed all the way by Japan.
There was an awful lot of expectation. You need to perform at the right time and some of them didn't. They didn't perform badly, but you can't just not do badly - you have to be great.
Britain have still not claimed a place on the podium in this event since the 1980 Games in Moscow.
The USA led from the second length with women's 200m backstroke gold medallist Missy Franklin ahead at the first changeover.
It was a lead never relinquished, with Rebecca Soni's breaststroke, Dana Vollmer's butterfly and Allison Schmitt's freestyle all ahead of the field.
While the United States stretched out in front, Great Britain struggled at the back of the pack.
Afterwards, Fran Halsall, who swam the anchor leg, told BBC Sport: "The support that we've had this week has been unbelievable, and the crowd have been unbelievable.
"I'm just a bit disappointed that I haven't been unbelievable this week."
Final results by Country
View full results for Women's 4 x 100m Medley Relay
Franklin, Soni, Vollmer, Schmitt, Bootsma, Larson, Donahue, Hardy
Seebohm, Jones, Coutts, Schlanger, Elmslie
Australian Olympic Team
Terakawa, Suzuki, Kato, Ueda