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Rohde was born in Hamburg and was the son of a doctor. Outside of antiquarian circles, Rohde is known today chiefly for his friendship and correspondence with fellow-philologist Friedrich Nietzsche. The two were students together in Bonn and Leipzig, where they were studying philology taught by Friedrich Wilhelm Ritschl. In 1872, Rohde became a professor at the University of Kiel. He later was professor in Jena (1876), Tübingen (1878) and finally Heidelberg, where he died in 1898 after suffering from a gradual decline in health.
His work, Der Griechische Roman und seine Vorläufer (1876), was considered by Mikhail Bakhtin to be "the best book on the history of the ancient novel", and it is still regarded as one of the greatest "monuments of 19th century classics scholarship in Germany".