Copper appears to be influencing the distribution and abundance of phytoplankton in marine environments, and cyanobacteria are thought to be the most sensitive of the phytoplankton groups to copper toxicity. By using growth assays of phylogenetically divergent clades, we found that coastal strains of marine Synechococcus species were more tolerant to copper shock than open-ocean strains. The global transcriptional response to two levels of copper shock were determined for both a coastal strain and an open-ocean strain of marine Synechococcus species using whole-genome expression microarrays. Both strains showed an osmoregulatory-like response, perhaps as a result of increasing membrane permeability. This could have implications for marine carbon cycling if copper shock leads to dissolved organic carbon leakage in Synechococcus species. The two strains additionally showed a common reduction in levels of photosynthesis-related gene transcripts. Contrastingly, the open-ocean strain showed a general stress response, whereas the coastal strain exhibited a more specifically oxidative or heavy-metal acclimation response that may be conferring tolerance. In addition, the coastal strain activated more regulatory elements and transporters, many of which are not conserved in other marine Synechococcus strains and may have been acquired by horizontal gene transfer. Thus, tolerance to copper shock in some marine Synechococcus strains may in part be a result of a generally increased ability to sense and respond in a more stress-specific manner.Marine Synechococcus and Prochlorococcus species are together thought to be responsible for at least 20% of global carbon fixation (25). They play such a significant role in the carbon cycle that it is essential to understand to which environmental stresses they are susceptible and how they respond. Cyanobacteria have been shown to be particularly sensitive to copper, for example, compared to other marine phytoplanktons (9). As a group, cyanobacteria have various levels of copper tolerance, with Prochlorococcus species thought to be more sensitive to copper than Synechococcus species (27). Within Synechococcus species, strain tolerance has been shown to vary (9), but those experiments with equilibrated copper levels were done prior to a better understanding of Synechococcus phylogenetic diversity.Applying a copper "shock" seems just as environmentally relevant as using equilibrated copper levels, since there are several mechanisms by which we could see sharp, rapid spikes of Cu 2ϩ concentrations in the surface waters where marine Synechococcus strains are found. Although the Cu 2ϩ concentration is generally low (10 Ϫ14 M) in the surface waters of the open ocean, it can increase by 3 or 4 orders of magnitude below the euphotic zone (12), and a mixing event could thus cause a sharp increase in Cu 2ϩ concentrations. Furthermore, in coastal environments, a sharp spike in free-copper levels can occur after a heavy rain due mostly to anthropogenic inputs (6). Finally, there is evidence that d...