In Washington, the CIA declined to comment, and officials at South Korea's National Intelligence Service did not answer repeated phone calls.
Asked about the possibility of US officials offering to engage in negotiations with North Korea over that rogue nation's missile buildup, White House Press Secretary Sean Spicer replied that for such talks to happen, Pyongyang would have to show signs of "good faith".
The North's ministry of state security said in a statement on Friday that the Central Intelligence Agency "assassination by use of biochemical substances including radioactive substance and nano poisonous substance is the best method that does not require access to the target".
"We will ferret out and mercilessly destroy to the last one the terrorists of the US CIA and the puppet IS of South Korea", the statement said, adding that the plot was tantamount to "the declaration of a war".
Reclusive North Korea warned this week that USA hostility had brought the region to the brink of nuclear war.
The North Korean statement comes during a period of tension on the Korean Peninsula over concerns that the North is preparing another nuclear test or missile launch, including a possible test of an intercontinental ballistic missile.
North Korea has a history of bombastic propaganda featuring unfounded claims.
South Korea has accused Pyongyang of assassination plots, too, most recently in February following the murder of Kim Jong Nam, allegedly at the hands of North Korean agents.
It has repeatedly threatened Kim with a military response to new tests of missiles and nuclear warheads, and sent warships and a nuclear submarine to Korean waters.
Bruce Klingner, a former Central Intelligence Agency analyst now at the Heritage Foundation think tank, said it could be the first time North Korea had accused the allies of an attempted assassination.
A North Korean newspaper said that the nation was "waiting for the moment it will reduce the whole of the USA mainland to ruins".
The Trump administration has said that all options, including military, remain on the table in dealing with North Korea, but that it is not pursuing a policy of regime change. That follows the killing of Kim's estranged half-brother Kim Jong-Nam at Kuala Lumpur global airport.