Metabolic stress disinfection and disinfestation (MSDD) is a postharvest treatment designed to control pathogens and arthropod pests on commodities that combines short cycles of low pressure/vacuum and high CO2 with ethanol vapor. Experiments were conducted to evaluate the effect of MSDD treatment on various life stages of Ceratitis capitata (Wiedemann), Mediterranean fruit fly; Bactrocera dorsalis Hendel, oriental fruit fly; and Bactrocera Cucurbitae Coquillett, melon fly, in petri dishes and in papaya, Carica papaya L., fruit. In some experiments, the ethanol vapor phase was withheld to separate the effects of the physical (low pressure/ambient pressure cycles) and chemical (ethanol vapor plus low pressure) phases of treatment. In the experiments with tephritid fruit fly larvae and adults in petri dishes, mortality was generally high when insects were exposed to ethanol and low when ethanol was withheld during MSDD treatment, suggesting that ethanol vapor is highly lethal but that fruit flies are quite tolerant of short periods of low pressure treatment alone. When papaya fruit infested with fruit fly eggs or larvae were treated by MSDD, they produced fewer pupae than untreated control fruit, but a substantial number of individuals developed nonetheless. This suggests that internally feeding insects in fruit may be partially protected from the toxic effects of the ethanol because the vapor does not easily penetrate the fruit pericarp and pulp. MSDD treatment using the atmospheric conditions tested has limited potential as a disinfestation treatment for internal-feeding quarantine pests such as fruit flies infesting perishable commodities.