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Um ano depois de resgatar Catherine Martin do horror que foi a cave de Buffalo Bill, a agente do FBI Clarice Starling recebe uma missão urgente da parte da mãe de Catherine, a Procuradora Geral Ruth Martin, para se juntar ao Violent Criminal Apprehension Program (VICAP) no âmbito da investigação de três homicídios em série.

Clarice Starling e a equipa VICAP são colocados no Tennessee onde o FBI cerca um grupo de milícia chamado “The Statesmen”.

Para provar a Krendler e à equipa VICAP que está apta para o serviço, Clarice tem de encontrar a chave psicológica que irá desencadear uma confissão da parte do suspeito dos três homicídios do rio.

Na sequência do homicídio de um suspeito, Clarice e a VICAP são investigados pelo rival de Krendler na Agência, Anthony Herman. Gera-se alguma fricção entre os dois quando Ardelia é recrutada para o ajudar.

Clarice é drogada por um serial killer que trabalha na área da medicina e fica numa cama de hospital com alucinações intensas.

Sidelined because of her harrowing ordeal with Marilyn Felker, Clarice goes to Ruth Martin to be reinstated and gets roped into having dinner at the Martin residence.

Clarice and Ardelia team up to investigate a deeply twisted cold case after the body of a missing teenager is found entombed in concrete. Also, Clarice wrestles with the knowledge that Krendler may know the man who attacked her while she was held captive.

Clarice feels an emotional tie to the victim when ViCAP investigates what appears to be the suicide of a medical student in the United States on a foreign visa. Also, Krendler secretly collects a DNA sample from the man he suspects attacked Clarice at Woodhaven.

After ViCAP links the River Murders to a pharmaceutical company, Clarice seeks help from Julia Lawson, the corporate accountant for the company, who refuses to work with the FBI, and with Clarice specifically. Also, Catherine goes outside for the first time since her rescue from Buffalo Bill, and Ardelia and Agent Garrett connect with a lawyer they hope will take on the Black Coalition's case against the FBI.

Catherine Martin escapes to Carneys Point, N.J., to confront Buffalo Bill’s mother, Lila Gumb. When Ruth recruits Krendler and ViCAP to track her down, Clarice volunteers to be the one to find Catherine before she commits a vile act and becomes a monster herself. Also, Julia continues to assist the ViCAP team’s investigation despite the huge personal risk.

Clarice zeroes in on the entity behind the River Murders, Alastor Pharmaceuticals. When Julia informs ViCAP of the impending sale of the company, ViCAP rushes to Alastor to prevent the purging of any incriminating evidence. Also, Clarice questions Alastor CEO Nils Hagen, who quickly changes the subject to Clarice’s relationship with his son, Tyson.

As ViCAP finally gets the green light to raid Alastor Pharmaceuticals, Clarice punches another FBI agent in a moment of rage, then willingly turns in her badge and gun. Also, the rest of the ViCAP team uncovers the whole truth about the River Murders, and Clarice unwittingly puts herself in mortal danger.

On the heels of ViCAP uncovering the secrets behind the River Murders case, Clarice is imprisoned in an abandoned animal testing facility where she finds trafficked women being held captive. As Clarice attempts to break from her captors and rescue all the women, ViCAP and Ardelia team up to locate her.