The air flow of an HVAC system for a multi-story building B is controlled by optimizing the pressure setpoint at the return air plenum PL-1 used for removing or recirculate air from the building, by measuring a pressure differential between the building B air and atmosphere A air at a sensor location P-2, computing a desired pressure differential between the building B air and atmosphere A air, based upon a computed stack effect pressure that is expected to develop at the sensor location on the building for the current inside and outside air temperature in the absence of mechanical action, and controlling the return air fan and damper D-1 to pressurize the air in at the sensor location to produce the desired pressure differential between the building B air and atmosphere A air at the sensor P-2 location. Air pressure is also controlled between specific rooms and adjacent rooms by control of the conditioned air or return air paths connected thereto.