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The Roman Empire had an immense impact on the development of viticulture and oenology. Wine was an integral part of the Roman diet and winemaking became a precise business. Virtually all of the major wine-producing regions of Western Europe today were established during the Roman Imperial era. During the Roman Empire, social norms began to shift as the production of alcohol increases. Further evidence suggests that widespread drunkenness and true alcoholism among the Romans began in the first century BC and reached its height in the first century AD. Viniculture expanded so much that by AD c. 92 the emperor Domitian was forced to pass the first wine laws on record, banning the planting of any new vinyards in Italy and uprooting half of the vinyards in the provinces in order to increase the production of the necessary but less profitable grain. (The measure was widely ignored but remained on the books until its 280 repeal by Probus.

Winemaking technology improved considerably during the time of the Roman Empire. Vitruvius noted how wine storage rooms were specially built facing north, « since that quarter is never subject to change but is always constant and unshifting », and special smokehouses (fumaria) were developed to speed or mimic aging. Many grape varieties and cultivation techniques were developed. Barrels (invented by the Gauls) and glass bottles (invented by the Syrians) began to compete with terracotta amphoras for storing and shipping wine. Following the Greek invention of the screw, wine presses became common in Roman villas. The Romans also created a precursor to today’s appellation systems, as certain regions gained reputations for their fine wines. The most famous was the white Falernian from the Latian–Campanian border, principally because of its high (~15%) alcohol content. The Romans recognized three appellations: Caucinian Falernian from the highest slopes, Faustian Falernian from the center (named for its one-time owner Faustus Cornelius Sulla, son of the dictator), and generic Falernian from the lower slopes and plain. The esteemed vintages grew in value as they aged, and each region produced different varieties as well: dry, sweet, and light. Other famous wines were the sweet Alban from the Alban Hills and the Caecuban beloved by Horace and extirpated by Nero. Pliny cautioned that such ‘first-growth’ wines not be smoked in a fumarium like lesser vintages.

Wine, perhaps mixed with herbs and minerals, was assumed to serve medicinal purposes. During Roman times, the upper classes might dissolve pearls in wine for better health. Cleopatra created her own legend by promising Antony she would « drink the value of a province » in one cup of wine, after which she drank an expensive pearl with a cup of the beverage. Pliny relates that, after the ascension of Augustus, Setinum became the imperial wine because it did not cause him indigestion. When the Western Roman Empire fell during the 5th century, Europe entered a period of invasions and social turmoil, with the Roman Catholic Church as the only stable social structure. Through the Church, grape growing and winemaking technology, essential for the Mass, were preserved. The oldest surviving bottle still containing liquid wine, the Speyer wine bottle, belonged to a Roman nobleman and it is dated at 325 or 350 AD.