Sulfate reduction is the most important process involved in the mineralization of carbon in the anoxic bottom waters of Mono Lake, an alkaline, hypersaline, meromictic Lake in California. Another important biogeochemical process in Mono Lake is thought to be sulfate-dependent methane oxidation (SDMO). However little is known about what types of organisms are involved in these processes in Mono Lake. Therefore, the sulfate-reducing and archaeal microbial community in Mono Lake was analyzed by targeting 16S rRNA, methyl-coenzyme M reductase (mcrA), adenosine-5'-phosphosulfate (apsA), and dissimilatory sulfite reductase (dsrAB) genes to investigate the sulfate-reducing and archaeal community with depth. Most of the 16S rRNA gene sequences retrieved from the samples fell into the delta-subdivision of the Proteobacteria. Phylogenetic analyses suggested that the clones obtained represented sulfate-reducing bacteria, which are probably involved in the mineralization of carbon in Mono Lake, many of them belonging to a novel line of descent in the delta-Proteobacteria. Only 6% of the sequences retrieved from the samples affiliated to the domain Euryarchaeota but did not represent Archaea, which is considered to be responsible for SDMO [Orphan et al. 2001: Appl Environ Microbiol 67:1922-1934; Teske et al.: Appl Environ Microbiol 68:1994-2007]. On the basis of our results and thermodynamic arguments, we proposed that SDMO in hypersaline environments is presumably carried out by SRB alone. Polymerase chain reaction (PCR) amplifications of the mcrA-, apsA-, and dsrAB genes in Mono Lake samples were, in most cases, not successful. Only the PCR amplification of the apsA gene was partially successful. The amplification of these functional genes was not successful because there was either insufficient "target" DNA in the samples, or the microorganisms in Mono Lake have divergent functional genes.