In May 2012, the National Institute for Occupational Safety and Health (NIOSH) received a request for technical assistance from the Duval County Health Department as part of its response to an ongoing tuberculosis (TB) outbreak among homeless persons in Florida. The request asked NIOSH to assess heating, ventilation, and air-conditioning (HVAC) systems and make recommendations to improve overall environmental controls at four homeless facilities with epidemiologic links to past or ongoing TB disease transmission. During an on-site evaluation of the City Rescue Mission-McDuff Campus homeless shelter complex in August 2012, we collected physical and ventilation measurements in all key areas of the facility. We focused on areas where guests typically congregate or spend significant amounts of time. We recorded the make and model number of all air-handling units (AHUs) providing supply air to the facility, and visually inspected the units. When possible, we measured the air flow rate through supply diffusers and return grilles. The ventilation systems in place could have contributed to airborne disease transmission among shelter guests. With the exception of some improper filter configurations and standing water inside one unit, the AHUs appeared adequately maintained and were fully operational. Unfortunately, none of the AHUs provided fresh outdoor air to the occupied spaces, as required by the Florida Building Code and the American Society of Heating, Refrigerating and Air-Conditioning Engineers design standards. In addition to alleviating odors and maintaining occupant comfort, outdoor air serves to dilute infectious aerosols, such as Mycobacterium tuberculosis droplet nuclei that are responsible for TB transmission. Since the TB outbreak began, City Rescue Mission-McDuff Campus has taken numerous steps to improve administrative controls, particularly when it comes to identifying guests showing signs and symptoms of TB. We recommend additional improvements to the administrative and environmental controls at the shelter. From a ventilation standpoint, we suggest that all occupied spaces at the shelter complex are supplied adequate amounts of outdoor air. In addition, we identified areas that could be converted for use as respiratory separation areas. These spaces could serve to separate guests suspected of having TB or other respiratory diseases from the remainder of the guest population, until medical evaluation, transport or treatment could be obtained. We also recommend developing a written infection control plan, HVAC operation and maintenance plan, and a written respiratory protection program. Having these plans/programs in place will help the shelter under normal operating conditions, and especially during any future outbreaks of respiratory disease.