ABSTRACTDespite years of successful isolation ofVibrio vulnificusfrom estuarine waters, beginning in 2007, it was extremely difficult to cultureV. vulnificusfrom either North Carolina estuarine water or oyster samples. After employing culture-based methods as well as PCR and quantitative PCR for the detection ofV. vulnificus, always with negative results, we concluded that this pathogen had become nearly undetectable in the North Carolina estuarine ecosystem. We ensured that the techniques were sound by seeding North Carolina oysters withV. vulnificusand performing the same tests as those previously conducted on unadulterated oysters.V. vulnificuswas readily detected in the seeded oysters using both classes of methods. Furthermore, oysters were obtained from the Gulf of Mexico, andV. vulnificuswas easily isolated, confirming that the methodology was sound but that the oysters and waters of North Carolina were lacking theV. vulnificuspopulation studied for decades. Strikingly, the apparent loss of detectableV. vulnificuscoincided with the most severe drought in the history of North Carolina. The drought continued until the end of 2009, with an elevated water column salinity being observed throughout this period and withV. vulnificusbeing nearly nonexistent. When salinities returned to normal after the drought abated in 2010, we were again able to routinely isolateV. vulnificusfrom the water column, although we were still unable to culture it from oysters. We suggest that the oysters were colonized with a more salt-tolerant bacterium during the drought, which displacedV. vulnificusand may be preventing recolonization.