Hayden Panettiere, Courteney Cox Return to Take Down a Ghostface Unlike Any Before in Scream VI Trailer

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Note: Some language and visuals in this trailer may be NSFW.

Ghostface is different this time around.

On Thursday, Paramount Pictures and Spyglass Media Group released the first full trailer for Scream VI, which marks the return of Scream 4's Kirby, played again by Hayden Panettiere, as well as Courteney Cox, who reprises her role of Gale Weathers.

The trailer teases Sam (Melissa Barrera) and Tara Carpenter's (Jenna Ortega) deadly run-in with Ghostface in New York City as they try to acquire the help of bystanders in a bodega.

Sam is then shown referencing her own connection to Scream's past — she's the daughter of the original 1996 movie's villain Billy Loomis (Skeet Ulrich) — as new characters meet with Kirby and Gale and discover something of a "shrine" to Ghostface.

Ghostface appears to single out Gale individually in the new trailer as the killer stalks her, giving way to a nerve-wracking confrontation between Sam, Tara and newcomer Josh Segarra's character, as well as their friends Chad (Mason Gooding) and Mindy (Jasmin Savoy Brown) on the subway during Halloween, surrounded by people in costumes.

RELATED: Scream 6 Will Be '100 Times Gorier,' Says Star Melissa Barrera: 'We're Going All Out'

Hayden Panettiere (“Kirby Reed”) stars in Paramount Pictures and Spyglass Media Group's "Scream VI."
Hayden Panettiere (“Kirby Reed”) stars in Paramount Pictures and Spyglass Media Group's "Scream VI."

Philippe Bossé/PARAMOUNT PICTURES

"This isn't like any other Ghostface," Panettiere's Kirby says in the trailer.

Later, Cox's Gale answers the phone and tells the mystery killer: "You know you're like the 10th guy to try this, right? It never works out for the dip-s--- in the mask." The killer responds, "Maybe. But there's never been one like me, Gale."

Courteney Cox (“Gale Weathers”) stars in Paramount Pictures and Spyglass Media Group's "Scream VI."
Courteney Cox (“Gale Weathers”) stars in Paramount Pictures and Spyglass Media Group's "Scream VI."

Philippe Bossé/PARAMOUNT PICTURES

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Neve Campbell, who has led the Scream films since the 1996 original, announced last year that she wouldn't be returning for the sequel after not receiving a suitable offer. (Spoiler alert: David Arquette's character Dewey was killed in the last film, so he's not expected to return.)

Campbell told PEOPLE in August, though, that she might still come back to the franchise in the future.

RELATED VIDEO: Hayden Panettiere on Returning to Acting with Scream Franchise: 'I Think It's a Fabulous Moment for Me'

"I don't know that I'm done for good," she said. "It would really depend on what they came to me with next. It would have to be different. It would have to be a different attitude, and I'm not sure that's going to happen."

Set in the Big Apple, the new Scream brings back the young cast introduced in 2022's Scream as they "leave Woodsboro behind and start a fresh chapter," according to a synopsis for the film. Barrera, 32, teased to Collider in December that the upcoming sequel is "potentially a hundred times gorier" than other films in the franchise.

Directed again by Matt Bettinelli-Olpin and Tyler Gillett, the film also stars Jack Champion, Henry Czerny, Liana Liberato, Dermot Mulroney, Devyn Nekoda, Tony Revolori, and Samara Weaving.

Scream VI is in theaters March 10.