America's leading presidential hopefuls are among those offering prayers, condolences and other global reaction to the worst mass shooting in U.S. history.
Presumptive Democratic presidential nominee Hillary Clinton told CNN, "We have to defend our country from the so-called lone wolves," a reference to individual perpetrators of deadly criminal acts. Clinton said U.S. residents "have the ability" to seize "a moment for all Americans to work together as one team" to combat terrorism and other violent acts.
Clinton called on citizens to reach out to Muslims in the U.S. "to help us defeat this threat." She cited the need for "common sense reform" of gun ownership laws.
Clinton's likely Republican presidential opponent, Donald Trump, predicted on CNN that domestic terrorism "will only get worse because we have very weak leadership." Trump renewed a call to stop the entry of Syrian refugees into the U.S., adding "they're coming in by the thousands."
Trump said Muslims have to report suspicious people, and he reiterated his support for strong gun ownership laws. "Gun owners more than ever need to protect themselves. If people in that [night club] had guns, you wouldn't have had the same tragedy," he said.
Reaction from the gunman's country of origin
Former Afghan president Hamid Karzai told VOA's Afghan service, "I fully understand the pain of the American people in this hour. We in Afghanistan have suffered for a long time and daily from such shootings and killings."
Early Sunday morning, 49 people were shot to death, and at least 53 others wounded in a shooting spree at a gay night club in Orlando. The gunman, Omar Mateen, was a U.S. citizen and the son of Afghan parents.
In Kabul, Afghan President Mohammad Ashraf Ghani strongly condemned the attack. "Targeting civilians is not justifiable under any circumstances whatsoever," Ghani said.
Afghanistan's Chief Executive, Abdullah Abdullah, expressed sympathy for families of the victims. He said “Terrorism and terrorists as foes of human beings are not representing any faith, religion, ethnicity and race.”
WATCH: Witness recalls club shooting
Condolences from around the world
German Chancellor Angela Merkel, speaking Monday in China said, "We have a heavy heart" over the fact that "the hatred and malignancy of a single person cost over 50 people their lives."
Britain's Queen Elizabeth sent a message to U.S. President Barack Obama that said, "Prince Philip and I have been shocked by the events in Orlando. Our thoughts and prayers are with all those who have been affected."
Elsewhere, the Holy See press office issued a statement, saying, "Pope Francis joins the families of the victims and all of the injured in prayer and in compassion. Sharing in their indescribable suffering he entrusts them to the Lord so they may find comfort."
A statement from the French president's office said Francois Hollande "condemns with horror" the mass killing in Florida, and "expresses the full support of France and the French with America's authorities and its people in this difficult time."
Palestinian Prime Minister Rami Hamdallah said the mass shooting is "a senseless act of terror and hate" and that "Palestinians stand with the American people in this difficult time."
Israeli Prime Minister Benjamin Netanyahu said Israel stands "shoulder to shoulder'' with the United States.
Chinese President Xi Jinping telephoned President Obama, Xinhua news agency reported, and expressed his "deepest sympathies, sincere condolences and deep grief for the victims."
Japanese Prime Minister Shinzo Abe condemned the attack, telling reporters, "Japan stands together with the people of the United States"and that "this despicable act of terror cannot be tolerated."
Australian Prime Minister Malcolm Turnbull said the shooting was "an attack on all of us -- on all our freedoms, the freedom to gather together, to celebrate, to share time with friends."
Prime Minister Najib Razak, of Muslim-majority Malaysia, said he was "horrified" by the Orlando shooting. "Islam abhors killing of innocent people," he tweeted.
“Our heart is with our American brothers,” tweeted Italian Prime Minister Matteo Renzi.
Canadian Prime Minister Justin Trudeau tweeted: "We grieve with our friends in the US & stand in solidarity with the LGBTQ2 community after today's terror attack."
Sadiq Khan, the mayor of London said, "I stand with the city of Orlando against hate and bigotry. My thoughts are with all the victims of this horrific attack."
“We are looking at a massacre that has no precedent in the history of the gay community,” Rome’s Gay Center spokesman Fabrizio Marrazzo told Italian news agency ANSA.
Ahmad Fawad Lami contributed to this report.