The land is close to where the teenager was last seen in the company of a convicted child killer.
A local farmer alerted police to disturbed ground in a field near the the village of Killen, in Co Tyrone.
Access to the scene, at the foot of a small valley in the rural hinterland, several miles outside Arlene’s hometown of Castlederg, has been sealed off since Tuesday.
A police cordon has been erected at the top of the single, narrow track that leads through fields to a secluded, derelict stone farmhouse concealed behind a huddle of mature trees.
A rundown metal barn is also behind the police tape.
Arlene, 15, disappeared in August 1994, after a night out across the border in Co Donegal.
She was last seen being driven down Scraghy Rd, close to the site of the new search, late at night, with paedophile Robert Howard.
Experts dressed in white forensic suits have spent much of the day inspecting the isolated site, clearing debris, such as branches and twigs, and placing some items into exhibit bags.
Grazing cattle may have eaten away the undergrowth to reveal the suspicious plot, believed to include stones.
The farmer who owns the land visited the site, but declined to speak publicly until the outcome of the search is known.
The Arkinson family are aware of the new activities. Det Chief Supt Raymond Murray, from the Police Service of Northern Ireland, said: “The family of Arlene Arkinson have been advised of this development, purely as a precautionary measure.
“It would be premature to draw any inference from this initial report, or the police response to it, at this time.”
Robert Howard was acquitted of the schoolgirl’s murder in 2005, by a jury that was not aware of his lengthy criminal history, which included killing another teenager, Hannah Williams, in south London, several years earlier.
Howard remained the prime suspect in the unsolved case until his death in an English prison last year.
More than 40 extensive searches have been conducted in forested areas, fire dams, reservoirs, and remote farmland in Tyrone, Fermanagh, and Donegal, but Arlene’s body has not been recovered.
Kathleen Arkinson has said she will never give up hope of finding her sister.
A long-running inquest into the circumstances of Arlene’s disappearance is expected to conclude hearing oral evidence, when it resumes in Belfast on Monday.
Ms Arkinson said the past few days had taken their toll.
She said: “It has been very difficult. But I am trying not to raise my hopes up.
“It has been so long and there have been so many let-downs. The difference this time is it’s so close to where Arlene was last seen. We just don’t know what to think, to be honest.
“The timing is also unbelievable, in the middle of the inquest. We’ll never get justice for Arlene. Justice has evaded her in every way, but I hope they can find her and we can get some closure.”