Some 46 bodies have been discovered inside a semitrailer in San Antonio, Texas, a common means of transportation for undocumented migrants entering the United States.
"At this time we have processed approximately 46 bodies that have been triaged and tagged and declared deceased," San Antonio Fire Chief Charles Hood told reporters.
He said 16 people had been taken to hospital alive and conscious — 12 adults and four children.
There were no initial details on the age or nationality of the deceased.
"The patients that we saw were hot to the touch, they were suffering from heat stroke, heat exhaustion, no signs of water in the vehicle, it was a refrigerated tractor-trailer but there was no visible working A/C unit on that rig," Mr Hood said.
Officials said three people were in custody over the incident.
"Tonight we are dealing with a horrific human tragedy," San Antonio Mayor Ron Nirenberg told a press conference.
Some 16 people had been taken to hospital alive and conscious — 12 adults and four children. Source: Getty / Jordan Vonderhaar
"So I would urge you all to think compassionately and pray for the deceased, the ailing, the families," he said.
"And we hope that those responsible for putting these people in such inhumane conditions are prosecuted to the fullest extent of the law."
San Antonio, which lies some 250 kilometres from the border with Mexico, is a major transit route for people smugglers.
It has also been gripped by a record-breaking recent heat wave, and temperatures in the area hit 39.5C on Monday.
The vehicle was found on a road near Highway I-35, a major US artery that stretches all the way to the border with Mexico.
A massive emergency operation was underway at the scene involving police, firefighters and ambulances.
According to San Antonio police chief William McManus, authorities were first alerted by an emergency call at about 5:50 pm.
"A worker who works in one of the buildings up here behind me heard a cry for help," he told reporters, "came out to investigate, found a trailer with the doors partially open, opened them up to take a look, and found a number of deceased individuals inside."
He said the probe had been turned over to the federal Department of Homeland Security.
'A better life'
Mexico's foreign minister, Marcelo Ebrard, called the incident a "tragedy" and said the Mexican consul was headed to the site.
Mr Ebrard said the nationalities of the victims were not yet known, but that two Guatemalans were among the survivors.
San Antonio was the site of a similar migrant tragedy in 2017, when 10 people suffocated to death in a sweltering trailer with broken air conditioning and clogged ventilation holes as they travelled into the United States.
Dozens more had been hospitalised with heat stroke and dehydration — with the truck believed to have been holding as many as 200 people, most of whom fled when it stopped in a parking lot. The truck driver later pleaded guilty to charges related to the deaths.
"Lord have mercy on them. They hoped for a better life," tweeted Gustavo Garcia-Siller, the archbishop of San Antonio, after news broke of Monday's awful discovery.
"Once again, the lack of courage to deal with immigration reform is killing and destroying lives."