The U.S. Border Patrol says the arrests took place Thursday at a checkpoint on Interstate 95 in the northern Maine town of Sherman.
Agents say a search of the men's vehicle uncovered plastic bags that held 2,999 80 milligram tablets of Oxycontin, a prescription painkiller that is popular among drug addicts. The street value of the pills is estimated at as much as $80 apiece.
Officials say they charged Damaso Sanchez and Geraldo Pineda-Sanch. Pineda-Sanch, of the Dominican Republic, was allegedly in the country illegally.
Both men are being held without bail at the Penobscot County Jail until a federal court date can be scheduled.
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