The eternal rivalry between cats and dogs got put on hold in the spirit of inter-species cooperation and do-gooder crimefighting in Ruff and Reddy, Hanna-Barbera's first production. The two main characters were Ruff, an adorable kitty in a blue bow and Reddy, a cute pooch with a Southern accent.

Ruff and Reddy faced a bevy of villains in their weekly adventures, including Harry Safari, Captain Greedy, and Western outlaws Killer and Diller. Professor Gizmo, a tiny inventor, often helped out the heroic duo. The action was formatted as serialized cliffhanger episodes, airing four such segments per half hour show.

The series also had live-action host Jimmy Blaine and his two bird puppets providing more entertainment between Ruff and Reddy segments. Blaine, Rhubarb the Parrot and Jose the Tucan were replaced by Captain Bob Cottle when the show was rerun after its cancellation.