The water trap seal under the sanitary appliances is the primary defense against the ingress of foul gases and odors. However, research on air pressure variation in a horizontal pipe of a single-stack drainage system is very limited. Thus a physical model study was conducted to investigate the air pressure variation in a horizontal pipe. Four parameters were studied that affect the pressure variation; that is, water flow rate, inlet height, ventilation condition and outlet condition. When the top of the vertical drainage stack and the outlet were fully open to the atmosphere, the flow in the horizontal pipe changed from free surface flow to slug flow at certain times. The mean values and magnitudes of pressure fluctuation at measuring points on the horizontal pipe increased with Qw but decreased along the horizontal pipe. The inlet height had relatively small influence on the pressure variation. Three ventilation conditions; that is, top fully open, half open and sealed, were tested, and a choking flow was formed in the vertical drainage stack and the pressure in the horizontal pipe decreased under the top sealed condition. Three outlet conditions; that is, outlet fully open, half submerged and fully submerged, were tested. The pressure in the horizontal pipe increased significantly under the outlet fully-submerged condition, which should be avoided in the actual operation by careful designing.