Synechocystis sp. strain PCC 6803 is a fresh-water, unicellular, non-nitrogen fixing cyanobacterium, containing a single bidirectional hydrogenase. This cyanobacterial hydrogenase has been purified as a pentameric enzyme and the corresponding structural genes, hoxEFUYH, are clustered together with three open reading frames (ORFs) of unknown function(s). In the present work, we present and summarize recent results in the regulation of the Synechocystis hydrogenase (e.g. H-2 itself is able to stimulate H2 evolution, a mutant without the diaphorase part of the bidirectional hydrogenase may develop a photooxidative processes in the absence of any detectable hydrogenase activity, and a higher hox transcript level in cells facing nitrogen starvation), and suggest a hypothesis on the direct involvement of the transcriptional regulator LexA as a mediator of the redox-responsive regulation of hox gene expression in Synechocystis PCC 6803. (c) 2006 International Association for Hydrogen Energy. Published by Elsevier Ltd. All rights reserved.