Voice cast
Burt Reynolds, Vic Tayback and Melba Moore are replaced by Charlie Sheen, Ernest Borgnine and Bebe Neuwirth respectively, but three characters were written out of the sequel. Anne-Marie was written out of the story, out of respect to her actress Judith Barsi who was murdered on July 25, 1988, alongside Flo, who would remain absent from the story as well. Killer, on the other hand, was withheld until the series.
Main characters
Charlie Sheen as Charles "Charlie" B. Barkin, a German Shepherd who returns from Heaven to find Gabriel's Horn. It is revealed that as a puppy, he ran away from home, a point he mentions to David to convince him to return home. Charlie Sheen replaced Burt Reynolds from the first film.
Jesse Corti as Charlie's singing voice.
Dom DeLuise as Itchiford "Itchy" Dachshund, Charlie's best friend. His motives are to find the horn and go straight back up to Heaven. Dom DeLuise was the only original actor to reprise his role from the first film.
Sheena Easton as Sasha la Fleur, an attractive Irish Setter, talented lounge singer and Charlie's love interest.
Adam Wylie as David, a disillusioned 8-year-old human boy and Sasha's owner. He believes that Charlie and Itchy are his guardian angels sent to get him back home safely. He replaces the role of Anne-Marie from the original film.
George Hearn as Red, a large beast-like demonic cat from Hell and the main antagonist. His goal is to imprison the dogs of Heaven, overthrow humanity, and permanently join Hell with the mortal world. To manipulate his victims, he disguises himself as a blinded elderly dog through his ability to shapeshift.
Bebe Neuwirth as Annabelle, the archangel Whippet in Heaven. She summons Charlie and Itchy to retrieve Gabriel's stolen Horn. She was voiced by singer Melba Moore in the first film.
Ernest Borgnine as Carface Caruthers, Charlie's arch-enemy, a Pit bull/bulldog mix
Supporting characters
Wallace Shawn as Labrador MC, the duplicitous MC at Sasha's lounge.
Hamilton Camp as Gavin, a Chihuahua. He waits for dogs especially a dog who puts on some weight to be healthy called Fluffy.
Dan Castellaneta as Tall Customs Dog
Pat Corley as Officer McDowell
Jim Cummings as Jingles, a Yorkshire Terrier who got kicked out of the sing-off, but was given the first place bone by Sasha.
Bobby Di Cicco as Tom, David's father.
Annette Helde as Claire, David's son pregnant step-mother.
Marabina Jaimes as Officer Reyes
Tony Jay as Reginald
Maurice LaMarche as Lost & Found Officer
Steve Mackall as Short Customs Dog
Kevin Michael Richardson as Ace the St. Bernard / Officer Andrews
