Gunmen ambushed a hotel and abducted two French citizens early Thursday, the first such attack in the area located far from the bases of al-Qaida-linked militants in the country's north.
Al-Qaida-linked fighters have often brought hostages to Mali from neighboring Niger, Mauritania and Algeria holding them in the desert for months.
But Thursday's kidnapping in the town of Hombori undermines the Malian government's position that most hostages are abducted elsewhere in the region where borders are porous.
"All these problems have always taken place a long way from us," said Maoulou Daou, a hotel owner in the town of Hombori where the French men were taken.
Daou said the two French men were abducted from another hotel, after the gunmen tied up the manager, guard and cook and went in search of the foreigners.
He said the French citizens were working on a site about 20 miles (35 kilometers) outside Hombori where a company is hoping to extract material to produce cement.
Military vehicles have been arriving from neighboring towns, and security personnel are surrounding Hombori.
In France, Foreign Minister Alain Juppe confirmed the kidnapping in comments shown on i-Tele television Thursday.
"Two of our compatriots were kidnapped in Mali in conditions that we do not know much about yet ... We are gathering information," Juppe said.
Thursday's kidnapping is the first in Mali of Westerners south of the enormous Niger River.
If the hostage-taking is linked to al-Qaida's North Africa branch _ the only group known to take hostages in this region _ they will have to be transported across the river before they can be moved to the group's bases in the far north of the country.
Al-Qaida in the Islamic Maghreb, once concentrated in its home base of Algeria, has rendered huge swaths of Mauritania, Mali, Niger and Algeria off-limits to foreigners. The militants are best known for kidnapping Westerners for ransom and are currently holding four French hostages, two Spanish and two Italians.
Associated Press writer Angela Charlton in Paris contributed to this report.