Police are assisting the Prison Service with a major search operation at Maghaberry Prison in County Antrim.
Inmates have been locked in their cells and all domestic and legal visits have been suspended for the day.
It is understood that it has been more than 10 years since a major search was carried out at the prison.
A Prison Service statement said the search was "in the interests of the safety of staff, prisoners and visitors".
Governor Steve Rodford said every effort was being made to keep disruption to a minimum.
"I hope to be in a position to return to normal regime levels as soon as is practically possible," he said.
"The safety and security of prisons are of paramount importance and this does require searches, both localised and extensive, to be carried out.
"I have commissioned such searches in my previous career in England and see this as an integral element of managing a high security prison."
Last month, traces of a component used in Semtex explosives were found in the cells of republican prisoners during searches.
The component was detected in swab tests taken during routine searches of two cells at Roe House.
At that time, a Prison Service spokesman said no Semtex was found during the operation.
Maghaberry is Northern Ireland's high security prison with republican and loyalist paramilitaries among its inmates.
The Prison Service said it regretted any inconvenience and that all visits lost would be re-scheduled.
A police spokesperson said that nothing had been found so far.