Martin Arrowsmith is from a tiny mid-western town. He goes to college and then to medical school in the largest town in the state. He begins to worship Gottlieb, Professor of Bacteriology, one of the few professors who is devoted to pure science instead of lucrative practice. Martin becomes Gottlieb’s assistant and annoys his professors and friends by constantly talking about methodology. He is engaged to Madeline, a rather dull graduate student in English. When he meets Leora, a nurse, he breaks his engagement to Madeline. Martin grows disenchanted with his career, leaves school, and wanders around the midwest. Finally, he marries Leora and returns to school. Now, however, he becomes a disciple of the Dean, Silva, whose science is much less precise and who is devoted to making people comfortable at all costs.

Martin sets up practice after graduation in Leora’s home town. The Swedish and German farmers find him invasive and unwilling to cater to their small-town expectations. When Martin misdiagnoses a case of smallpox, he is forced to leave town. He has by then found a new hero, Gustave Sondelius, who fights plagues abroad and returns to America to lecture. Sondelius finds him a job in a larger town as an assistant to Dr. Almus Pickerbaugh, Director of Public Health. Pickerbaugh writes popular poems against sidewalk spitting and alcohol but does little else. The town loves him. He becomes a senator and Martin takes over the department. He quickly makes enemies of the very people Sondelius pleased. He also returns to research. Between annoying the upper crust with his brusqueness and annoying the farmers by closing their diseased dairies, he is soon drummed out of town.

He is then hired as a pathologist at the Rouncefield Clinic, where he does meaningless, repetitive work. His old mentor, Gottlieb, saves him by getting him a position at the McGurk Institute in New York. The Institute is very rich and gives scientists a chance to work without the interruption of patients or a need for practical application. Martin returns to Gottlieb’s principles and discovers a cure for bubonic plague. The Institute, which is not free from economic interests, sends him off to the tropical island of St. Hubert to test his material and save the population.

Martin is determined to conduct a controlled trial. When his wife and Sondelius both die of the plague, however, he injects everyone, saves the island, and returns to New York. Gottlieb has dementia and can neither blame nor forgive Martin for his lack of scientific aplomb. Martin marries an heiress and briefly lives the rich life he always dreamed of, but finds that his new wife will not let him work. Finally, he joins a friend who has built a laboratory in Vermont and happily returns to research.