The incident took place in a train, which left Salem last evening to Chennai.
Around Rs 342 crore cash was moved in 226 boxes in a train from Salem, via Viruduchalam, to RBI Chennai, said sources.
Of these, two boxes were found to be tampered and money spilled out from the boxes and point of entry was found to be a hole made at the roof of coach.
The quantum of money looted is not yet known. When contacte,d RBI's regional office refused to share any information stating that they would come out with an official statement.
Sources said that RPF has filed a case and the matter is being investigated by a team headed by Sub Inspector Vijayakumar.