Police believe some people may be buried under the debris after the 6.55am explosion at the Askariya mosque but there were no confirmed figures.
The shrine contains the tombs of two revered Shia imams, both descendants of the Prophet Muhammad, and is among Iraq's most sacred sites for Shia Muslims.
Tradition says the shrine, which draws Shia pilgrims from throughout the Islamic world, is near the place where the last of the 12 Shia imams, Mohammed al-Mahdi, disappeared. Al-Mahdi, known as the "hidden imam," was the son and grandson of the two imams buried in the Askariya shrine.
Shias believe he is still alive and will return to restore justice to humanity. An attack at such an important religious shrine would constitute a grave assault on Shia Islam at a time of rising sectarian tensions in Iraq.
National Security Adviser Mouwafak al-Rubaie said armed men wearing special forces uniforms broke inside the shrine and seized the guards, including policemen, responsible for protecting the site. The gunmen planted the explosives and fled.
Al-Rubaie blamed extremists represented by the al-Qaida terror network and Sunni militant group Ansar al-Sunnah for the explosion, which he told the Al Arabiya television aimed "to pull Iraq toward civil war."
The Sunni Endowment, a government organization that cares for Sunni mosques and shrines, condemned the blast and said it was sending a delegation to Samarra to investigate what happened.
Following the blast, US and Iraqi forces surrounded the shrine and began searching houses in the area. Five police officers responsible for protecting the mosque were taken into custody, said Col. Bashar Abdelallh, chief of police commandoes in Samarra.
In the Shia holy city of Najaf, the country's most revered Shia cleric, Grand Ayatollah Ali al-Sistani, ordered seven days of mourning and called on Shias to hold peaceful protests in their home provinces and not go to Samarra, aides said.
Residents of Najaf began closing their shops and were gathering in the city's 1920 Revolution Square for a demonstration to condemn the Samarra attack.
Thousands of demonstrators gathered near the shrine, waving Iraqi flags, Shia religious banners and copies of the Muslim holy book, Quran. Shia leaders in Baghdad's Sadr City neighborhood called for demonstrations against the blast.
"This criminal act aims at igniting civil strife," said Mahmoud al-Samarie, a 28-year-old builder who was among the crowd in this city 95 kilometers (60 miles) north of Baghdad. "We demand an investigation so that the criminals who did this be punished. If the government fails to do so, then we will take arm and chase the people behind this attack."
Religious leaders at other mosques and shrines throughout the city denounced the attack in statements read over loudspeakers from minarets.
The shrine contains the tombs of the 10th and 11th imams, Ali al-Hadi who died in 868 A.D. and his son Hassan al-Askari who died in 874 A.D and was the father of the hidden imam.
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