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The squirrel monkey named Gordo survived a 300-mile journey into space and then travelled more than 1,500 miles in the rocket until it dropped in the South Atlantic.
A technical problem with the recovery gear meant a parachute failed to open and the nose-cone sank taking Gordo with it. The US Army abandoned the search after six hours.
Gordo's condition was monitored by the Pentagon, which said the monkey suffered no significiant adverse physical effects during the time it was weightless.
The 50 ton Jupiter AM-13, which usually carries intermediate-range missiles, was fired by the army from Cape Canaveral in Florida this morning. The flight lasted 15 minutes.
Gordo, a South American breed of monkey about one foot (30cm) tall and weighing between two and three pounds (1-1.5kg), was chosen because it has a similar anatomical make-up to man and is also very sensitive to changes in temperature.
US defence officials say the breathing of the monkey slowed down after take-off and its pulse became slightly irregular, but both quickened as the missile gained speed and once the nose-cone was beyond the pull of Earth's gravity they returned to normal.
Gordo wore a leather-lined plastic helmet. He was strapped on a moulded rubber bed with his knees drawn up to resist the strains of gravity.
The monkey was insulated against temperature changes with foil and fibre glass. He had a thermometer under his armpit, a microphone listened to his heartbeat and other instruments detected his breathing.
There have been angry protests from animal rights groups about the decision to send Gordo into space.
The American Society for Prevention of Cruelty to Animals said only inanimate objects should be used for such tests. The British Royal Society for the Prevention of Cruelty to Animals also expressed "grave concern and apprehension".
But the US Defense Department insists the experiment was an invaluable step in preparing for man's first venture into space. They say the monkey's make-up is so similar to man's there is now no reason humans cannot undertake similar flights in future.
Gordo is not the first animal to have ventured into space, but he is the first primate to have flown so high.
In May 1959, the United States sent a pair of monkeys, Able and Baker, into space on a Jupiter missile. They were the first living creatures to be successfully recovered after a trip into space.
Although Able died in June 1959, monkey Baker survived until 1984.
Later in 1959 and in early 1960 there were further experiments involving a pair of monkeys named Sam and Miss Sam.
Soviet scientists decided against using monkeys for test flights. Their scientific research - published in September 1958 - suggested the monkeys would have to be anaesthetised and the anaesthetic would interfere with test results.
They had already launched a dog, Laika, into space in November 1957. At the time, Russian scientists claimed the dog had survived a week in orbit but later reports show it died shortly after take-off from overheating and panic.
But it was the Russians who won the race to launch the first man into space. Major Yuri Alexeyevich Gagarin orbited the Earth for nearly two hours on 12 April 1961.
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