Manuela Velasco, who plays the journalist Angela, had just graduated in communications and said she was very nervous in front of a camera; it was precisely her mistakes and inexperience during the casting that convinced the directors to give her the role, as they were looking for a young, inexperienced journalist rather than a seasoned one.

Most of the actors were cast without a complete script, on simple improvisation, and never received the full synopsis of the film or knew in advance which scenes they would shoot or what would happen in them.

Patient zero, Tristana Medeiros, described as possessed, is actually played by a man, Javier Botet, an actor with Marfan syndrome which gives him a wasted body allowing him to play all sorts of creatures.

For the role of little Jennifer, the directors were looking for a child capable of considerable physical strength since she was to be the only infected child in the story; casting videos show the actress screaming and violently pushing away adults holding her, as in the scene where she becomes infected.

The film was shot in chronological order and in very long uncut sequence shots, one of which lasts 22 minutes without interruption; the only visible cuts are due to the momentary stopping of the camera, its fall or rewinding.

The shoot, entirely carried out in Barcelona (at number 34 of the Rambla de Catalonia) in great secrecy, lasted only about twenty days, with a very limited budget of 1.5 million euros, filmed on high-definition digital cameras and mobile phones for a real-time rendering.

The directors sometimes gave the actors contradictory or incomplete instructions in order to provoke maximum spontaneity; most of the actors were, for example, not informed in advance that the firefighter would fall down the stairwell, one of the scenes considered most difficult to shoot.

Two alternative endings were written solely to deceive the actors and preserve the secret about the film's true ending; they were revealed only on the second DVD of the collector's edition released on October 23, 2008.

The film's trailer shows no extract from the film itself but a camera filming the terrified reactions of spectators in the cinema, an original way of suggesting the horror that the film provokes.

An American remake titled Quarantine, released in October 2008, recreates the film shot by shot with American actors, but abandons the supernatural explanation for the infection in favor of a virus designed as a biological weapon by eco-terrorists.

With a very modest budget, the film was a great success, ranking among the 100 most profitable films of the 2000s outside the United States (96th position) and earning over 33 million dollars, attracting over 1,420,000 spectators in Spain and nearly 786,455 admissions in France.