Aquaculture necessitates a range of husbandry and handling procedures that induce or exacerbate stress. The relationship between environmental stress and suppression of immune responses has been defined in a range of invertebrate models. In the current study, we investigated the effects of antifouling practices on PO (phenoloxidase activity), which is associated with host defense in mature pearl oysters. The stressors included the use of a cleaning machine (high pressure water jets), being struck with a chisel to remove fouling, a combination of the cleaning machine and chiseling, and exposure to air. We also investigated the effects of exposure to air on PO activity in juvenile pearl oysters. PO activity declined significantly (by 56%, relative to the control) 48. h after oysters were chiseled (p. <. 0.05). Similarly, PO activity was inhibited in oysters exposed to jets and oysters treated with a combination of the jets and chisel (by 43% and 40% decrease, respectively). Ninety-six hours after treatment PO activity increased significantly (p. <. 0.05) in oysters exposed to the combination treatment (2.61 fold increase) and to jets alone (2.06 fold increase). Exposure to air alone initially resulted in a significant decline (by 43%) in PO activity after 48. h (p. <. 0.05), and then a subsequent increase (2.61 fold increase) after 96. h (p. <. 0.05). In contrast, PO activity in juvenile oysters remained significantly elevated relative to controls at both 24 and 96. h after exposure to air (p. <. 0.05). These data indicate that modulation of PO activity may be a useful indication of stress in pearl oysters.