Pearl River is an adventure story about Indians, war, friendship, and love in the historic setting of the campaign for New Orleans during the War of 1812. A Virginia-born physician, Glenn Buchanan, returns from surgical study in Paris to join Andrew Jackson's army in the defense of New Orleans. He returns by way of the Gulf of Mexico and arrives at the mouth of the Pearl River to look for Jackson's army. Walking upriver through the swamps, he discovers a half-breed Choctaw woman in labor and delivers her dead baby. The two survive a hurricane and subsequent flood en route to her village near the headwaters of the Pearl River. Walking down the Natchez Trace with his Choctaw guide, Chunkey, Glenn learns at LeFleur's Bluff that Jackson's army is just east of the Pearl River, building roads. Abandoning the Natchez route to New Orleans, he travels back down the Pearl by dugout canoe, and joins the army. After participating in the Battle of New Orleans, Glenn treats one of his army officer friends who is wounded in a duel over the daughter of a sugar plantation owner. Encounters with alligator, bobcat, panther, and river boatmen, as well as hunting and fishing for food, enliven Glenn's travels. He uses his skills as a surgeon and physician in his treating of multiple injuries and illnesses. The story is intertwined with authentic war history.