John Dolittle, MD, is a respected physician and quiet bachelor living with his spinster sister Sarah in the small English village of Puddleby-on-the-Marsh.

His love of animals grows over the years and his household menagerie eventually scares off his human clientele, leading to loss of wealth.

His fortunes rise and fall again after a crocodile takes up residence, leading to his sister leaving in disgust with the intention of getting married, but his fame in the animal kingdom spreads throughout the world.

On the way to the monkey kingdom, his band is arrested by the king of Jolliginki, a victim of European exploitation who wants no white men travelling in his country.

In appreciation, the monkeys find the pushmi-pullyu, a shy two-headed gazelle-unicorn cross, whose rarity may bring Dr. Dolittle money back home.