Major international airlines are canceling and re-routing flights in the Middle East after Iran fired more than a dozen missiles at two Iraqi military bases that house US forces.

Air France (AFLYY), Lufthansa (DLAKY), Malaysia Airlines and Taiwan’s EVA Air said they were avoiding the airspace above Iran and Iraq. Singapore Airlines (SINGF) said it would not fly over Iran.

The Federal Aviation Agency meanwhile restricted commercial US flights “from operating in the airspace over Iraq, Iran, and the waters of the Persian Gulf and the Gulf of Oman.” Authorities in Russia recommended the country’s airlines avoid the same areas.

Meanwhile, a Boeing 737 flown by Ukraine International Airlines crashed near Imam Khomeini Airport in Tehran early on Wednesday, according to Iran’s semi-official news agency ISNA.

The jet had 176 passengers and crew aboard, according to ISNA. A Boeing (BA) spokesperson said the company is “aware of the media reports out of Iran and we are gathering more information.” Among those killed were 82 Iranians and 63 Canadians, according to Ukrainian officials.

Ukrainian Prime Minister Oleksiy Honcharuk told reporters in Kiev that it was “too early” to establish the cause of the crash. Ukraine’s embassy in Iran removed from its website a statement which said that terror or rocket attacks had been ruled out as causes of the plane crash.

Escalating tensions between the United States and Iran are making it tougher for airlines to fly over the Middle East, where huge chunks of airspace are already off limits because of political rivalries or war.

The attacks by Tehran were retaliation for a US airstrike last week that killed a top Iranian general. A US official told CNN that there were no initial reports of any US casualties from the attack.

Some airlines reacted by canceling flights. Lufthansa said it would not fly to Tehran or Erbil, a city in northern Iraq that is home to one of the bases hit in the Iranian missile strike. Emirates canceled flights between Dubai and Baghdad, where the Iranian general was killed.

Qatar Airways and Turkish Airlines said they were conducting flights as usual. British Airways (ICAGY) and Virgin Atlantic said they were monitoring the situation, but not yet diverting flights.

For commercial airlines and freight carriers, flight restrictions mean taking the long way around, costing time and money. And nowhere is the disruption more acute than the Middle East.

Airlines have avoided flying over Syria in recent years, staying well clear of airspace patrolled by military aircraft. But they have also, at various points, avoided parts of Iran and Iraq. A civil war has put Yemen off limits since 2015, and airlines also avoid the North Sinai, where Egypt is battling Islamist militants.

Yet a huge number of flights from European airports such as London, Amsterdam and Frankfurt must still traverse the region on their way to Asian destinations like Bangkok and Singapore.

The additional miles flown to avoid trouble spots mean higher costs for airlines, which together spend $180 billion a year on jet fuel.