McDuff, a ghost of an old English sheep dog, lived in/haunted the home of Dr. Calvin Cambell, a veterinarian. Also living in the home were Kimmy, Calvin's little sister, and Mrs. Osgood, the house keeper. Amos Ferguson was the Cambell's neighbor and Squeaky was his young nephew. Besides being able to talk to other animals, McDuff could also talk to Calvin. However, Calvin was the only human who could hear McDuff - which led to a variety of wacky situations.