Nakienones A-C and nakitriol, a series of reactive cytotoxic metabolites, were isolated from dead and necrotic branches of stony coral (Acropora sp.) which were completely covered with a gray-black mat of cyanobacteria (Synechocystis sp.). Their structures were determined spectroscopically by interpretation of 2D-NMR experiments, including HMBC and NOESY, and by comparison with model compounds. Marine algal overgrowths have recently been established as a contributing factor leading to the destruction of hard-coral communities. As part of our ongoing survey of marine algae for biomedical potential, we discovered at a depth of -1 to -2 m several large (diameter 3-4 m), nearly concentric, zones of Synechocystis sp. overgrowth on a coral reef in the waters off Yonaha at Nakijin Village, Okinawa. The coral beneath this mat was darkened and free of obvious signs of animal tissue. While we are unable to prove that this overgrowth caused the death of the subtending coral, we strongly suspect this to be the case due to the observed growth pattern of the cyanobacteria. From this microalgal-coral assemblage, we have isolated four new cytotoxic C11 metabolites, nakienones A-C (1, 3, 5) and nakitriol (2), which may be involved in the chemical ecology of this interaction.