In the early 18th century, the spleen was a curious object. It was not only an organ the function of which had baffled both ancient and modern authors, but it was also the name and the alleged seat of a type of melancholy many contemporaries believed it was an epidemic disease in England. This article analyses a lecture on the spleen published in 1723 by the Lincolnshire physician and antiquarian William Stukeley. Placing it in the context of the quarrel between the ancients and the moderns, the paper traces the role that the classical tradition had in Stukeley’s endeavour. It argues that his selective reading of the classics sought to recover a prisca sapientiawhich favoured a theory of the spleen and its place in the microcosm with relevant theological implications. Furthermore, the ancients provided Stukeley with arguments and lessons to fight the modern spleen epidemic.