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In fr. 81 DK, Empedocles says that “wine is water from the bark (?) rotten in wood” (οἶνος ἀπὸ φλοιοῦ πέλεται σαπὲν ἐν ξύλῳ ὕδωρ). This apparently simple definition has received less attention than it deserves. Perhaps the first question that we must address is: What is this “wood”? Modern editors have given two answers: Wright reasonably takes it to be the wood of a cask or vat in which juice is fermented into wine; Gallavotti, Bollack, and Diels say that it is the wood of the vine. The relevant evidence has not yet been adequately presented: in light of it, we will see that this wood can only be the living vine. Yet what, then, is the “wine”? Is Empedocles talking about grape juice? Or did he think that wine was already in substance wine—i.e., an intoxicant—prior even to the ripening of the fruit, and therefore also prior to the vigorous frothing or “boiling” (cf. Greek ζέω, Latin ferveo > fermentum) that we now understand to result from yeast digesting sugars and producing carbon dioxide along with alcohol and other biproducts? Interpreting this fragment thus leads us to a remarkably under-examined problem in the history of natural philosophy: Did anyone in antiquity (or indeed before Pasteur) fully recognize that wine only becomes intoxicating after fermentation? Drawing on the discussions of the fragment in Aristotle and Plutarch, along with other fragments and testimonia as well as other authors including Plato, Plutarch, and Francis Bacon, this paper aims at a thorough reassessment of the evidence for the interpretation of this fragment. Its conclusions are that Empedocles’ wine is “rotted” within the living wood of the vine, and that Empedocles was not referring to the unintoxicating juice of the grape, but what he thought was already wine.