Family Guy fans reacted in shock, dismay and anger Sunday night after Brian, the Griffins' family dog and a fan-favourite regular character, was killed off and replaced with a new pet in short order.

In the episode titled "Life of Brian," the talking dog voiced by show creator Seth MacFarlane is hit by a speeding car while crossing the road. A lengthy hospital scene shows Brian pass away surrounded by the rest of the Griffin family.

Brian has been a series staple since the show debuted in 1999. An articulate talking dog frequently at odds with his family, fans perhaps knew him best as the travelling companion of the megalomaniacal baby Stewie Griffin on numerous episodes.

Fans reacted with shock and disbelief at Brian's death. FOX's official Family Guy Twitter account posted a picture of Brian after the episode aired. The hashtags #familyguy and #RIPBrian later reached the top of the social media network's trending lists.

True to Family Guy's breakneck pacing, it introduced Vinnie, a new dog voiced by The Sopranos' Tony Sirico, in the same episode.

Family Guy executive producer Steve Callaghan told E! Online that the idea to kill off a main character "caught fire" quickly once it was pitched, and Brian seemed the least painful choice.

"It seemed more in the realm of reality that a dog would get hit by a car, than if one of the kids died," said Callaghan. "As much as we love Brian, and as much as everyone loves their pets, we felt it would be more traumatic to lose one of the kids, rather than the family pet."

Assuming the character death remains permanent – show creator MacFarlane can presumably return to the role whenever he wants – Brian Griffin joins the list of deceased cartoon pets including Seymour the dog from Futurama and at least four cats named Snowball from The Simpsons.