Information technology (IT) is becoming increasingly pervasive throughout society as more data is digitally processed, stored, and transferred. The infrastructure that supports IT activity is growing accordingly, and data center energy demands have increased by nearly a factor of four over the past decade. This dissertation investigates how building design and operation influence energy use and indoor air quality in data centers and provides strategies to improve both design goals simultaneously. As an initial step toward understanding data center air quality, measurements of particle concentrations were made at multiple operating northern California data centers. Ratios of measured particle concentrations in conventional data centers to the corresponding outside concentrations were significantly lower than those reported in the literature for office or residential buildings. Estimates using a material-balance model match well with empirical results, indicating that the dominant particle sources and losses--ventilation and filtration--have been characterized. Measurements taken at a data center using economizers show nearly an order of magnitude increase in particle concentration during economizer activity. However, even with the increase, the measured particle concentrations are still below concentration limits recommended in most industry standards. The research proceeds by exploring the feasibility of using economizers in data centers while simultaneously controlling particle concentrations with high-quality air filtration. Physical and chemical properties of indoor and outdoor particles were analyzed at a data center using economizers and varying levels of air filtration efficiency. Results show that when improved filtration is used in combination with an economizer, the indoor/outdoor concentration ratios for most measured particle types were similar to the measurements when using conventional filtration without economizers. An energy analysis of the data center reveals that, even during the summer months, chiller savings from economizer use greatly outweigh the increase in fan power associated with improved filtration. These findings indicate that economizer use combined with improved filtration could significantly reduce data center energy demand while providing a level of protection from particles of outdoor origin similar to that observed with conventional design. The emphasis of the dissertation then shifts to evaluate the energy benefits of economizer use in data centers under different design strategies. Economizer use with high ventilation rates is compared against an alternative, water-side economizer design that does not affect indoor particle concentrations. Building energy models are employed to estimate energy savings of both economizer designs for data centers in several climate zones in California. Results show that water-side economizers consistently provide less energy savings than air-side economizers, though the difference in savings varies by location. Model results also show that conventional limits on humidity levels in data centers can restrict the energy benefits of economizers. The modeling efforts are then extended to estimate national data center energy use. Different size data centers are modeled to represent the national variation in efficiency and operation of associated mechanical equipment. Results indicate increased energy efficiency opportunities with larger data centers and highlight the importance of temperature setpoints in maximizing economizer efficiency. A bottom-up modeling approach is used to estimate current (2008) United States data center energy use at nearly 62-70 billion kWh annually. The model indicates that more about 65-70% of this energy demand can be avoided through energy efficient IT and cooling infrastructure design, equivalent to an annual energy efficiency resource of approximately 40-50 billion kWh available at a national level. Within the context of greenhouse gas emissions, benefits can be significantly increased by incorporating site location into energy-efficient design strategies. (Abstract shortened by UMI.). [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]