The killing of 16 villagers by an American soldier in Afghanistan's south could hurt Washington's efforts to reach a strategic pact with Kabul to allow a long-term US presence in the country.
The United States wants to maintain advisers there as it tries to wind down the war.
The Strategic Partnership Agreement currently being negotiated is a key part of that strategy.
An Afghan government official says the latest killings could delay the signing of the agreement.
The soldier shot dead at least 16 civilians, mostly women and children, and wounded others after entering their homes in Kandahar province.
Nine children are among those killed in the incident.
US officials have warned of possible reprisal attacks.
The soldier left his base early on Sunday morning to attack village homes, the BBC reports. In one he woke all 11 family members, killed them with a single shot to the head and then burned the bodies.
He then repeated the act in two more houses before giving himself up to the US authorities.
Afghan President Hamid Karzai has condemned the attack as "intentional murders" and has demanded an explanation.
The White House voiced "deep concern", promising a thorough investigation, and Nato-led forces in Afghanistan promised a "rapid" inquiry.
US President Barack Obama has extended his deepest condolences, and says one rogue soldier is not representative of the entire American military. He called Mr Karzai to express his shock and sadness at the killings.
The man is said to have suffered a nervous breakdown before the killings, the BBC reports.
Nato's spokesperson Brigadier General Carsten Jacobson says there is no reason to believe there was a larger conspiracy involved in the shootings.
In Kandahar's Panjwai district, people have gathered near the base to protest about the killings, and the US embassy is advising against travel to the area.
Anti-American sentiment is already high in Afghanistan after soldiers burnt copies of holy book the Koran at a Nato base in February, apparently in error.
US officials have apologised repeatedly for the incident in Kabul but failed to quell a series of protests and attacks that killed at least 30 people and six American troops.
The shooting rampage has prompted the Republican presidential hopeful Newt Gingrich to question the US approach to Afghanistan, saying too many young American lives have already been lost.
Mr Obama has set a 2014 deadline for the withdrawal of the 130,000-member US-led Nato force from Afghanistan.