In 1848 an English physician, Nathaniel Trennant, accepts an offer to serve as doctor on a ship carrying immigrants to America. When arriving in Baltimore, Trennant stumbles onto its slave market and witnesses the horrors of human bondage. One night in a boardinghouse he discovers under his bed a runaway slave. Disturbed and angered by the selling of human lives, he offers to help the young man escape, a criminal action that will put the fugitive slave and physician into flight from both the law and opportunistic slave hunters.

Traveling by foot, horse, stage, canal boat, and steamer, Nathaniel and Nicodemus explore the backcountry and forge a deep friendship as they encounter a host of memorable characters who reveal the nature of the American experiment, one still in its early stages but already under the stress of social injustices and economic inequities.