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During the fermentation process, yeast consumes juice sugars and produces two byproducts: alcohol and carbon dioxide. If winemakers want a sparkling wine, they ferment under pressure to dissolve carbon dioxide bubbles into the wine (see "Sparking Wine"). "Still" wines result when winemakers allow the carbon dioxide to escape. Accordingly, grapes with high sugar levels have the potential to produce higher-alcohol or sweeter wines if sugar remains after fermentation. The entire process takes place in four to seven days for red wines and several weeks–and sometimes months–for the cooler, slower white wine fermentations. Fermentation vessels include vats made of oak, stainless steel and cement.

Before fermentation, winemakers may make adjustments to the juice. When grapes grow in cool climates or vintages produce insufficient sugar, winemakers may add sugar to the juice to increase final alcohol levels—a practice called "chaptalization" or "enrichment". On the other hand, if the location or year is hot, winemakers may add tartaric acid–the acid found naturally in grapes–to ensure the wine is balanced and refreshing.

At a certain temperature, fermentation occurs naturally when the yeast found in the grape skins comes in contact with juice sugars. However, wild yeasts die before alcohol levels reach 5 percent. Accordingly, many winemakers launch and complete fermentation using cultured yeast that can ferment all the sugars and reach higher alcohol levels, usually 12 to 16 percent. Others allow wild yeast to start fermentation, which is then completed by indigenous yeasts that live within the winery and its equipment.

Fermentation continues until either the yeast consumes all the sugar, alcohol levels kill the yeast or the winemaker halts the process by chilling or filtering the must. When yeast consumes all the sugars, the result is a dry wine, whereas residual sugar may remain to produce "off-dry" (slightly sweet) or sweet wine.

Winemakers must control oxygen levels, which is necessary to both launch and complete fermentation. In some cases, winemakers employ a process called "micro-oxygenation" by bubbling in small amounts of oxygen through the must to keep things on track and add complexity. Sometimes used later in the winemaking process, micro-oxygenation can facilitate development during barrel aging.

Fermentation produces heat, and certain temperatures are necessary to keep the fermentation going. Overly high temperatures can spoil the wine, destroy flavor compounds and lead to excessive and bitter tannin extraction. Insufficient warmth inhibits color and flavor extraction, creates undesirable flavors and may stop fermentation, which could potentially spoil the wine as well. Winemakers ensure the right temperature by controlling cellar temperatures and/or employing special tanks or "jackets" around tanks that regulate temperatures.

For red wine fermentation, the optimal temperature range is between 68 and 90 degrees Fahrenheit, while white wines do best from 50 to 64 degrees. Lower temperatures produce lighter, fruitier red wines, and higher temperatures produce more color, flavor and body. Winemakers sometimes ferment white wines at the lower end of their temperature range to keep them fruity.

Red wines demand that winemakers also manage the skins, which float to the top of the vat, dry out and form a cap that excludes oxygen and prevents color and flavor extraction. Winemakers use technologies or manual labor to "punch down" the cap back into the juice a few times a day, pump juice from the bottom of the vat over the cap or submerge the cap using a screen near the top of the tank.

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