QX is a fatal disease in Sydney rock oysters (Saccostrea glomerata) that results from infection by the protistan parasite, Marteilia sydneyi. Since 1997, the New South Wales Fisheries Service has bred S. glomerata for resistance to QX disease. The current study shows that the QX resistance breeding program has selected oysters with enhanced phenoloxidase (PO) activities. The third generation of QX-selected oysters was compared to S. glomerata that had never been selected for disease resistance. PO enzyme assays showed that oysters bred for resistance had significantly higher PO activities than the non-selected population. There was no difference between populations in the activities of a variety of other enzymes. Native polyacrylamide gel electrophoresis identified a novel form of PO in QX-selected oysters that contributes to their enhanced PO activities. This novel form of PO may represent a specific QX disease resistance factor.