ABSTRACT: Black band disease (BBD) consists of a cyanobacterial-dominated, sulfide-rich microbial mat that migrates across coral colonies, degrading coral tissue. The mat contains diverse bacteria that include photoautotrophs (cyanobacteria), sulfate-reducers, sulfide-oxidizers, and organoheterotrophs. BBD sulfate-reducers contribute to BBD pathobiology by production of sulfide, which causes coral tissue lysis and death, and the cyanotoxin microcystin is produced by BBD cyanobacteria. Here we used a model system of coral fragments to investigate the roles of sulfide and microcystin in BBD by exposure to the metabolic inhibitors sodium molybdate and 3-(3’,4’-dichlorophenyl)-1,1-dimethylurea (DCMU), which inhibit sulfate reduction and oxygenic photosynthesis, respectively. Exposure of BBD inocula to sodium molybdate prior to inoculation prevented infection of healthy fragments but did not prevent continued band migration and coral tissue lysis by active BBD infections. Exposure to DCMU did not inhibit either the initiation of BBD or continued migration of active BBD. Exposure of healthy coral fragments to sulfide, purified microcystin, and a combination of both revealed that both microcystin and sulfide are toxic to coral and act synergistically. Measurement of growth of bacteria isolated from BBD and the healthy coral surface mucopolysaccharide layer (SML) during exposure to microcystin revealed that growth of relatively more BBD than SML isolates was stimulated, although effects were not uniform and the majority exhibited no effect. Our results indicate that sulfide is required for initiation of BBD, both microcystin and sulfide are involved in BBD pathobiology, and microcystin may structure the BBD bacterial community.