“We respect the court’s decision,” Stephanie Kercher, a sister of the slain student, told journalists after an appeals court overturned the murder convictions of Ms. Knox, who had been sentenced to 26 years in prison, and her former boyfriend, Raffaele Sollecito, who had been sentenced to 25 years.

Ms. Kercher said, the family was disappointed and surprised, but still awaiting the “full truth,” which they believe could emerge in the next phase of the case.

Prosecutors in Perugia said shortly after Monday night’s verdict that they would appeal the reversal to Italy’s highest court. Francesco Maresca, the Kercher family’s lawyer, predicted on Tuesday that the legal wrangling “will be very difficult.”

In December 2009, Ms. Knox, of Seattle, and Mr. Sollecito had been found guilty of killing Ms. Kercher during what prosecutors described as a drug-fueled sex encounter that spiraled out of control.

All three were students in Perugia at the time. Lyle Kercher, the slain girl’s brother, said Monday’s reversal left the family “obviously looking at this again, and a decision that seemed so certain two years ago has been so emphatically overturned now. It obviously raises further questions.”

Mr. Kercher emphasized that a third man, Rudy Guede, a Perugia resident born in the Ivory Coast, had been sentenced to 16 years for the murder in a separate trial. In its final ruling on the case, Italy’s highest court found that Mr. Guede had acted with others in committing the crime, although the court did not identify Ms. Knox or Mr. Sollecito as conspirators.

“The courts agree that he wasn’t acting alone,” Mr. Kercher said. “If the two people released really were not guilty, we are left wondering what really happened.”

“It feels very much as though we are back to square one,” he said.

Monday night’s decision was unlikely to quell the doubts of many — especially in Britain and Italy — who believe that prosecutors had solved the case when they arrested Ms. Knox and Mr. Sollecito on Nov. 6, 2007, five days after Ms. Kercher’s naked and bloody body was found in the apartment she shared with Ms. Knox.

“Amanda and Raffaele Acquitted, Rage Explodes,” read a headline in the local edition of the Rome daily Il Messaggero, a reference to the mob of young Perugia residents who crowded around the courthouse on Monday, and chanted “for shame, for shame,” after the verdict.

Ms. Knox left Italy on Tuesday morning, on a flight to London, news agencies reported.

At a news conference on Monday, before the verdict was announced, members of the Kercher family said they had come to Perugia to make sure that the memory of Meredith was kept alive.
“We want to be present and remember Meredith in a city she loved,” Stephanie Kercher said of her sister, who had arrived in the Umbrian town to study just two months before she was murdered. Meredith, she said, “was a lovely girl, and a great friend,” who “had always been there for everyone.”

The Kercher family had been suing Ms. Knox and Mr. Sollecito for damages, but this request was automatically dropped with the court ruling.

“What happened to my daughter Meredith is every parent’s nightmare that something awful will happen to their child,” Arlene Kercher, Meredith Kercher’s mother, said at the news conference on Tuesday. And while she acknowledged that the families of the defendants had also suffered over the past four years, she said it was too soon to offer forgiveness or have a dialogue.

“In this moment it is impossible to speak, let’s see over the years what will happen,” she said.