Mexican drug lord Joaquin Guzman, known as El Chapo or "Shorty", used an elaborate tunnel to break out of a maximum security prison, officials say.
His escape route from Altiplano jail was more than 1.5km (1 mile) long and had ventilation and stairs, the national security commissioner said.
Eighteen guards are being questioned.
Guzman was last seen in the showers of the jail on Saturday. It was the second time he had escaped from a top security prison.
In 2001 he broke out by hiding in a laundry basket after bribing prison officials.
He had been serving a sentence of more than 20 years after being arrested in Guatemala in 1993.
His recapture in 2014 was hailed as a victory for Mexico's government.
Analysis: Juan Paullier, BBC Mundo
Guzman's escape is a huge embarrassment to the government of President Enrique Pena Nieto.
Earlier this year, his administration dismissed concerns that Guzman could escape for a second time, but the government's worst nightmare has unfolded.
Since Mr Pena Nieto took office in 2012, authorities have detained or killed numerous top drug lords. However, this escape is seen as a mockery of the Mexican prison system and shows the difficulty in keeping one of the country's most powerful criminals behind bars.
It seems unlikely that the prison break took place without some form of inside help.
A manhunt has been launched. But even if he's recaptured many here wonder what's the point of putting him back in a Mexican jail.
Officials say that Guzman's escape was discovered when officers checked his cell in the jail, which is near the capital, Mexico City.
They found a hole around 10m (32ft) deep with a ladder, which led to the tunnel, with lighting, ventilation and stairs.
It came to an end at a construction site outside the prison walls, security commissioner Monte Alejandro Rubido said at a news conference.
A motorcycle was also discovered, which police believe was used to transport tools and remove earth from the space.
A manhunt has been launched and flights suspended at a nearby Toluca airport.
Mr Pena Nieto has ordered a full investigation to establish whether any officials helped Guzman escape.
"I was profoundly shocked by the news. This is an affront to the Mexican state," he said.
Guzman's wealth is estimated at $1bn (£630m).
His rise to head of the Sinaloa cartel made him the world's most wanted drug trafficker. It smuggles huge amounts of cocaine, marijuana and methamphetamine into the United States.
Before his recapture in 2014, the US state department had offered a reward of up to $5m (£3.2m) for information leading to his arrest.
Attorney General Loretta E. Lynch issued a statement saying the US government shared Mexico's concern regarding the escape of Guzman.
"In addition to his crimes in Mexico, he faces multiple drug trafficking and organized crime charges in the United States," she said.
She said the US government is ready to co-operate with Mexico to help recapture Guzman.