Microbial electrolysis cells (MECs) represent an emerging technology that uses heterotrophic microbes to convert organic substrates into fuel products, such as hydrogen gas (H-2). The recent development of biophotovoltaic cells (BPVs), which use autotrophic microbes to produce electricity with only light as a substrate, raises the possibility of exploiting similar systems to harness photosynthesis to drive the production of H-2. In the current study we explore the capacity of the cyanobacterium Synechocystis sp. PCC 6803 to generate electrons by oxygenic photosynthesis and facilitate H-2 production in a two-chamber bio-photoelectrolysis cell (BPE) system using the electron mediator potassium ferricyanide ([Fe(CN)(6)](3-)). The performance of a wild-type and mutant strain lacking all three respiratory terminal oxidase activities (rto) was compared under low or high salt conditions. The rto mutant showed a decrease in maximum photosynthetic rates under low salt (60% lower P-max than wild-type) but significantly increased rates under high salt, comparable to wild-type levels. Remarkably, rto demonstrated a 3-fold increase in (Fe[CN](6))(3-) reduction rates in the light under both low and high salt compared to the wild-type. Yields of H-2 and efficiency parameters were similar between wild-type and rto, and highest under high salt conditions, resulting in a maximum rate of H-2 production of 2.23 +/- 0.22 ml H-2 l(-1) h(-1) (0.68 +/- 0.11 mmol H-2 [mol Chl](-1) s(-1)). H-2 production rates were dependent on the application of a bias-potential, but all voltages used were significantly less than that required for water electrolysis. These results clearly show that production of H-2 using cyanobacteria is feasible without the need to inhibit photosynthetic O-2 evolution. Optimising the balance between the rates of microbial-facilitated mediator reduction with H-2 production may lead to long-term sustainable H-2 yields.