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This is the third book in The Chronicles of Barsetshire, the first two being The Warden and Barchester Towers; however, although some characters from the first two books are referred to, there is no need to read/ listen to them first to enjoy Dr. Thorne.

It is mainly concerned with the romantic problems of Mary Thorne, niece of Doctor Thomas Thorne (a member of a junior branch of the family of Mr. Wilfred Thorne, who appeared in Barchester Towers), and Frank Gresham, the only son of the local squire, although Trollope as the omniscient narrator assures the reader at the beginning that the hero is really the doctor.

Themes of the book are the social pain and exclusion caused by illegitimacy, the nefarious effects of the demon drink and the difficulties of romantic attachments outside one's social class. The novel also gives a vivid picture of electioneering and all the barely legal shenanigans that accompany the event. Most of the action takes place in a village of Barsetshire and a country house not far off.When their father dies, Doctor Thomas Thorne and his younger, ne'er-do-well brother Henry are left to fend for themselves. Doctor Thorne begins to establish a medical practice, while Henry seduces Mary Scatcherd, the sister of stonemason Roger Scatcherd. When Scatcherd finds out that Mary has become pregnant, he seeks out Henry and kills him in a fight.

While her brother is in prison, Mary gives birth to a girl. A former suitor offers to marry her and emigrate to the United States to start a new life but refuses to take the baby. Doctor Thorne persuades her to accept the generous offer, promising to raise his niece. He names her Mary Thorne but wishing neither to have her illegitimacy made public nor to have her associate with the uncouth Roger Scatcherd, he keeps her birth secret. He tells Scatcherd that the baby had died.

After his release, Scatcherd rises quickly in the world as a railway project undertaker. In time, his skills make him extremely rich. When he completes a seemingly-impossible important project on time, he is made a baronet for his efforts. Throughout his career, he entrusts his financial affairs to Doctor Thorne. When Thorne becomes the family doctor to the Greshams, he persuades Scatcherd to lend ever growing sums to the head of the family, the local squire, who has troubles managing his finances. Eventually, much of the Gresham estate is put up as collateral.