Beginning in Summer 2013 and continuing to present, sea star wasting disease (SSWD) has affected 15 asteroid species on the North American Pacific Coast. The disease is characterized by behavioral changes, appearance of lesions, loss of animal turgor, limb amputation and ultimately animal death, where animals dramatically degrade (æmeltingÆ). The cause of the disease was not known. We investigated the cause of this disease by comparing the composition of viruses, bacteria and eukaryotic microorganisms inhabiting diseased and healthy tissues of sea stars. Bacteria and eukaryotic microrganisms were not different between diseased and healthy tissues, and these groups were not observed by microscopy. Most viruses inhabiting sea star tissues were those that infect bacteria and other microorganisms. Amongst viruses that infect animals, like sea stars, a single virus- known as the sea star associated densovirus- was better represented in diseased tissues than in healthy tissues. We sought to examine the association between the presence and load of this virus and the disease through quantitative molecular methods, and determined that it was significantly higher and more prevalent in diseased than healthy tissues. We inoculated healthy sea stars with viruses from diseased animals and induced the same disease symptoms as seen in diseased animals. This was repeated twice, confirming that viruses were the cause of the disease. Hence, given our observation of viruses causing the disease and our observation that SSaDV was associated statistically with the disease, we determined that SSaDV was the most promising candidate causative agent of the disease. We detected SSaDV in plankton and sediments around diseased sea stars, suggesting it may move between animals via free particles and form a reservoir in sediments. Gene expression analyses comparing diseased and healthy tissues suggest that sea stars respond to viral infection by inducing autocatalytic death processes. Historical analyses of museum specimens suggest that the virus has been present in the Pacific since at least 1942, and that it is present on the Atlantic coast as well. Taken together, our results suggest that sea star wasting disease is most likely caused by SSaDV, which has undergone recent change to cause enhanced mortality. Last Modified: 01/13/2015 Submitted by: Ian Hewson