KABUL—North Atlantic Treaty Organization troops opened fire Monday on a bus packed with civilians in the southern Afghan province of Kandahar, killing at least four and wounding 18 others, officials said.

Civilian casualties have long sapped Afghan support for NATO's fight against the Taliban, and officials in Kandahar reacted angrily to news of Monday's killings. The deaths come at a particularly delicate time: the U.S. and its allies are planning a major offensive against the Taliban in Kandahar in the coming months, and commanders have repeatedly stressed that success depends upon earning the support of the province's people and its government.

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Afghan police stand guard as protesters burn tires during a demonstration on the outskirts of Kandahar city on Monday.
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A spokesman for the provincial governor, Zelmai Ayubi, said the bus was traveling west from Kandahar city, the capital of the province, when it came up behind a NATO convoy around dawn Monday.

When the bus—which was believed to be carrying between 50 and 60 people—failed to heed warnings to stop, the troops opened fire, he said.

Mr. Ayubi and other officials said some of the wounded were taken to hospitals in Kandahar and others were sent to the better-equipped hospital at Kandahar Air Field, the massive coalition base on the edge of the city.

NATO said it had dispatched a team to investigate the shooting. But it would not say if alliance troops were involved in the shooting.

Afghanistan's Interior Ministry also said it had ordered the Kandahar police to investigate the shooting.

Aware of the damage done by civilian deaths, the top U.S. and NATO commander in Afghanistan, U.S. Army Gen. Stanley McChrystal, has made reducing civilian casualties a top priority. Last year, he issued strict orders on when foreign troops could open fire in an effort to reduce the number of civilians killed.

The result was a roughly 30% drop last year in the number of Afghan civilians slain by coalition forces. But such deaths still remain a regular occurrence, stoking anger among Afghans who have grown weary and frustrated after nine years of war.