The attack at Camp Qargha, a base west of the capital, Kabul, killed who is believed to be the highest-ranking US officer to die in the nearly 13-year war and comes as foreign troops prepare to withdraw by the year's end.
While details remained murky about what sparked the attack, it showed the challenges still remaining in Afghanistan, a nation that's known three decades of war without end.
He did not offer a motive for the assault.
US officials identified the dead US officer as a major general. One US official said about half of the wounded were Americans. That officials spoke on condition of anonymity as the officials were not allowed discuss the information by name ahead of an official announcement.
Germany's military said 15 NATO soldiers were wounded in an assault launched "probably by internal attackers." The wounded included a German brigadier general, who the German military said was receiving medical treatment and was "not in a life-threatening condition."
It is "an act by the enemies who don't want to see Afghanistan have strong institutions," Karzai said in a statement.
In a statement sent to journalists, Taliban spokesman Zabihullah Mujahid praised the "Afghan soldier" who carried out the attack, as well as a police officer in Paktia province who shot at NATO forces earlier today. He did not claim the attacks.
Qargha is known as "Sandhurst in the Sand", referring to the famed British military academy as British forces oversaw building the officer school and its training programme.
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