Pacific oyster mortality syndrome (POMS), which is caused by the virus OsHV-1, has devastated oyster farming globally and threatens the $225 million shellfish aquaculture industry on the U.S. West Coast. Lacking typical treatment or control measures, POMS progresses rapidly, causing up to 100% losses; once detected in a growing area, the virus remains and spreads. On the other hand, breeding for POMS resistance has successfully diminished mortalities in France, Australia, and New Zealand, where POMS is established. This Phase I project aims proactively to gain a scientific understanding of mechanisms of genetic resistance to POMS in order (1) to accelerate identification of resistant animals in commercial, as well as natural, West Coast populations and (2) to establish a POMS-resistant but otherwise diverse base population for further genetic improvement. We will generate inbred Pacific oyster families at our breeding facility in Hawaii, challenge offspring from these families with different viral strains in a biosecure laboratory in Arizona, and expose other siblings from these same families to the less virulent virus in Tomales Bay, California. The most-resistant and most-susceptible families will be propagated for crosses and gene-mapping studies in Phase II, which will enable dentification of genetic markers for POMS-resistance.