Microcosm experiments simulating the occurrence of early mortality syndrome/acute hepatopancreatic necrosis disease (EMS/AHPND) in white shrimp production ponds were performed in 30-L aquariums. Healthy white shrimp, Litopenaeus vannamei, were reared in aquariums containing EMS/AHPND-free hatchery or pond water. Raw pond sludge, collected from shrimp ponds where EMS/AHPND had occurred, was added to some test aquariums, while others were treated with sterilized pond sludge. In some aquariums, water pH was increased from 7.5 to 8.8. Microcosms with stable pH (around 7.5) and/or autoclaved sludge served as controls. The combination of raw sludge and increased pH induced EMS/AHPND and killed white shrimp, whereas raw sludge/stable pH and autoclaved sludge/increased pH combinations did not affect healthy shrimp. Thus, EMS/AHPND outbreaks are due not only to the causative agent but also to environmental stresses such as pH fluctuation. These findings contribute to improved management in shrimp production farms.