Middlemarch's main narrative follows the path of three marriages: Rosamund Vincy to Tertius Lydgate, Fred Vincy to Mary Garth and Dorothea Brooke to Will Ladislaw. Beyond that, Middlemarch bears very little conventional summarising because so much and so little happens at the same time. There is a huge cast of characters but no definite glorious acts; only a detailed examination of creeping causes.

The book opens with the young and idealistic Dorothea marrying the elderly scholar Mr Casaubon. Meanwhile another young and idealistic character has come to the town: Lydgate, who intends to implement medical reforms. Lydgate is drawn into marriage with the blonde, beautiful and terminally vain Rosamund Vincy... whose brother is trying to court the resolutely plain Mary Garth. But Fred has no money and instead hopes that his frail wealthy uncle will see fit to leave him his fortune. His uncle has other ideas and Fred is left without money or a profession. Mr Casaubon meanwhile dies abruptly (and fortunately) of a heart condition. Dorothea is left free but lonely and realises a growing attraction to the (also young and idealistic) Will Ladislaw, who was a distant cousin of Mr Casaubon. Pride and misunderstanding conspire to keep them apart especially when Dorothea finds Will with Rosamund... who has gradually destroyed her marriage with Lydgate with her silent stubbornness. Lydgate's medical reforms are regarded with growing suspicion by the town as he runs further and further into debt.

Will however has never been interested in Rosamund and declares his love to Dorothea who gives up her money to marry him; Fred finds work for Mary's father and finally convinces her he is a man worth marrying. Yet Rosamund unfortunately triumphs over Lydgate and forces him to leave Middlemarch and become a doctor to the rich in Bath.

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