Hundreds of protesters chanted anti-US slogans and burned a US flag to protest a remark by Democratic US presidential hopeful Barack Obama saying that, if elected, he might order military strikes in Pakistan against al-Qaeda.
The protests followed comments by Pakistani officials calling Obama's comments irresponsible.
Obama's comment turned up the heat on already simmering anger among Pakistanis about the issue, after senior Bush administration officials said last week they too would consider such strikes if intelligence warranted them.
Further inflaming the situation was a comment by Tom Tancredo, a Colorado Republican whose bid for the White House is considered unlikely to succeed, that the best way he could think of to deter a nuclear terrorist attack on America would be to threaten to retaliate by bombing the holiest of Islamic sites, Mecca and Medina.
In Miran Shah, a major town in the lawless region that borders Afghanistan, about 1,000 tribesmen condemned recent Pakistani military operations in the area and vowed to repel any U.S. attack.
"We are able to defend ourselves. We will teach a lesson to America if it attacks us," local cleric Maulvi Mohammed Roman told the rally.
In Karachi, Pakistani's largest city, about 150 people chanted slogans against the US, Obama and Tancredo at a demonstration organized by Mutahida Majlis-e-Amal, a coalition of six hard-line religious parties. Protesters set fire to a US flag.
"Those who are talking about attacking our holiest places are committing blasphemy. The punishment for this offense is death, and death only," said coalition lawmaker Mohammed Hussain Mahanti.
In a major policy speech Wednesday, Obama said as president he might order strikes in Pakistan's tribal zone to get terrorists, including those responsible for the Sept. 11 attacks on the US.
"There are terrorists holed up in those mountains who murdered 3,000 Americans. They are plotting to strike again," Obama said. "If we have actionable intelligence about high-value terrorist targets and President Musharraf will not act, we will."
Top officials in the government of Pakistan President General Pervez Musharraf, a key U.S. ally in the fight against terrorism, bristled at Obama's comment.
"It's a very irresponsible statement, that's all I can say," Foreign Minister Khusheed Kasuri said. "As the election campaign in America is heating up we would not like American candidates to fight their elections ... at our expense."
In Washington, the State Department reacted with unusual venom to Tancredo's remarks.
Republican presidential contender Mitt Romney said Obama's remarks were "ill-considered."