The U.S. Food and Drug Administration (FDA) recently issued an advance notice of proposed rulemaking (ANPRM) seeking input into the potential development of a product standard to lower nicotine in combustible cigarettes to minimally or non-addictive levels. This presentation reviews agricultural practices and environmental factors and their effect on accumulation of nicotine, the major alkaloid in tobacco. Nicotine is synthesized in the roots of the tobacco plant and is subsequently transported to leaves and stems where it accumulates. Any agricultural practice that increases the size of the root system in relationship to the size of the plant will, in general, increase the amount of nicotine accumulated in the tobacco leaves. Conversely, any agricultural practice that increases the size of the plant in relationship to the root system will, in general, decrease the amount of nicotine accumulated in the tobacco plant leaves. Other agricultural practices that have an effect on nicotine accumulation are: nitrogen rates, plant populations, topping (expressed as number of leaves per plant), and sucker control. Other factors contributing to the amount of nicotine accumulated in tobacco are environmental, among which water (in the form of rainfall), is the most significant. During an extremely dry year, tobacco will be higher in nicotine and lower in sugar content. In an extremely wet year, tobacco will be lower in nicotine and higher in sugar content. Other environmental factors include: soil type, root injury, and day length. This presentation will provide an overview of the various agricultural and environmental factors that have the greatest impact on nicotine accumulation, and will provide insight into some of the challenges that the tobacco industry and growers would face in the event of a very low nicotine product standard.