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Detained in the south-east coastal city of Valencia, Safwan Sabagh and Abdelkrim Beghadali, both 41, had been previously arrested in March in connection with the same investigation but released for lack of evidence.
The ministry said their fingerprints were found in the apartment in the Madrid suburb of Leganes in which seven people suspected of involvement in the bombings blew themselves up as the police closed in on April 3.
Their prints, and well as two phone numbers used by Sabagh, were also found in a Skoda car used by the bombers, responsible for nearly 200 deaths, and later found in Leganes, the ministry said.