At least 46 people have been found dead in an abandoned truck on the outskirts of San Antonio, Texas.
A fire official said 16 people, including four children, had also been taken to hospital.
The survivors were “hot to the touch” and suffering from heat stroke and heat exhaustion.
San Antonio, which is 250km from the US-Mexican border, is a major transit route for people-smugglers.
Human traffickers often use trucks to transport undocumented migrants after meeting them in remote areas once they have managed to cross into the United States.
“They had families… and were likely trying to find a better life,” San Antonio Mayor Ron Nirenberg said. “It’s nothing short of a horrific, human tragedy.”
Emergency responders initially arrived at the scene at about 18:00 local time after responding to reports of a dead body, San Antonio fire chief Charles Hood told reporters.
“We’re not supposed to open up a truck and see stacks of bodies in there. None of us come to work imagining that,” he said.
He added that the vehicle, which had been abandoned by its driver, had no working air conditioning and there was no drinking water inside it.
San Antonio’s climate is blisteringly hot in the summer months, with temperatures there reaching 39.4C on Monday, and it is suspected that the victims likely died from heat exhaustion and dehydration.
San Antonio’s far south side is a corridor with two main highways connecting the city to Texas border towns.
Mostly rural communities, a few junkyards and a handful of developing neighbourhoods in this part of San Antonio make it easy for a truck this size to go unnoticed, until it doesn’t.
Texas’s Republican Governor Greg Abbott blamed US President Joe Biden for the deaths, describing them as a “result of his deadly open border policies”.
Beto O’Rourke, the Democratic candidate running against Mr Abbott, said the reports were devastating and called for urgent action to “dismantle human smuggling rings and replace them with expanded avenues for legal migration”.
Immigration is a contentious political issue in the United States, where in May a record 239,000 undocumented migrants were detained crossing into the country from Mexico – many travelling along extremely risky and unsafe routes.
US law enforcement officials are on track to exceed the record 1.73 million border arrests made in 2021, with large numbers of people continuing to cross from Central American countries such as Honduras, Guatemala and El Salvador.
Fleeing poverty and violence in Central America, many of the undocumented migrants end up paying huge sums of cash to people-smugglers to get them across the US border.