Dark Spot Syndrome (DSS) typically manifests in scleractinian corals as lesions of varying color, size, shape and location that can result in skeletal changes and tissue death. A causative agent for DSS has not yet been identified. The objective of this study was histological and ultrastructural comparison of the cellular and skeletal characteristics of DSS-affected and healthy Siderastrea siderea and Agaricia agaricites. The greater resolution possible with transmission electron microscopy (TEM) revealed microbial activity and tissue changes not resolvable utilizing histology. DSS-affected tissue had less integrity, with increasing cellular degradation and vacuolization. A high concentration of electron dense inclusions, which appear to be zymogen granules, was concentrated in the calicodermis and adjacent gastrodermal layer. Numerous endolithic fungal cells were observed directly adjacent to the calicodermis in DSS-affected S. siderea. Numerous unidentified endolithic cells were observed directly adjacent to the calicodermis in DSS-affected A. agaricites. These observations suggest that the coral may be using a digestive enzyme as a defensive mechanism against endolithic cellular invasion
