Police in a small town in Massachusetts are hoping to test the DNA of the entire adult male population as they try to solve a three-year-old murder.
A murder inquiry in Germany once looked at 16,000 samples
Truro officials say the 790 men in the town have a right to refuse but those who do so will be closely checked.
The initiative has been prompted by slow progress in the case of fashion writer Christa Worthington, who was killed in her home in January 2002.
The broad sweep of the test is alarming civil rights campaigners.
American Civil Liberties Union spokesman Barry Steinhardt told the New York Times that a refusal to undergo the tests in itself aroused suspicion.
"They're not very effective and they're certainly not voluntary," he said. "It's either give a sample or you're a suspect. It turns the classic American concept of 'innocent until proven guilty' on its head."
There are also concerns among some campaigners that negative samples could be kept for use in the investigation of other crimes.
Police chose dates close to the third anniversary of the killing in the hope of narrowing the possible field of suspects to permanent, winter residents.
They have been approaching local men in shops and the town post office, where many residents pick up their mail, the New York Times says.
Christa Worthington, 46, was found stabbed to death in her bungalow with her two-year-old daughter clinging to her. Traces of semen were found on the body.
The three-year investigation has made little significant progress so far.
Mass DNA testing has yielded some results in the UK and Germany but has been less successful in the US.
Six years ago, German police investigating the rape and murder of an 11-year-old girl matched one man's sample to evidence prompting a confession.
More than 16,000 samples were taken, in what is thought to have been the biggest mass test to date.