The instant invention provides methods and apparatus for disinfecting a space, e.g., a hospital room, using chlorine dioxide. One aspect of the invention provides an apparatus for disinfecting a space. The apparatus includes: a chlorine dioxide gas generator a sensor adapted and configured to measure the relative pressure inside the space and outside the space and a computer operatively connected to the sensor and the chlorine dioxide generator, the computer adapted and configured to control the chlorine dioxide generator to operate only when the space is under negative pressure as compared to outside the space. Another aspect of the invention provides a method of disinfecting a space. The method includes: setting an apparatus as described herein in the space and allowing the apparatus to determine if the space is under negative pressure. If the space is under negative pressure, the apparatus generates chlorine dioxide gas to disinfect the space.