Abstract The stratified (meromictic) water column of alkaline and hypersaline Mono Lake, California, contains high concentrations of dissolved inorganic arsenic (∼200 μmol/L). Arsenic speciation changes from arsenate [As (V)] to arsenite [As (III)] with the transition from oxic surface waters (mixolimnion) to anoxic bottom waters (monimolimnion). A radioassay was devised to measure the reduction of 73 As (V) to 73 As (III) and tested using cell suspensions of the As (V)-respiring Bacillus selenitireducens , which completely reduced the 73 As (V). In field experiments, no significant activity was noted in the aerobic mixolimnion waters, but reduction of 73 As (V) to 73 As (III) was observed in all the monimolimnion samples. Rate constants ranged from 0.02 to 0.3/day, with the highest values in the samples from the deepest depths (24 and 28 m). The highest activities occurred between 18 and 21 m, where As (V) was abundant (rate, ∼5.9 μmol/L per day). In contrast, sulfate reduction occurred at depths below 21 m, with the highest rates attained at 28 m (rate, ∼2.3 μmol/L per day). These results indicate that As (V) ranks second in importance, after sulfate, as an electron acceptor for anaerobic bacterial respiration in the water column. Annual arsenate respiration may mineralize as much as 14.2% of the pelagic photosynthetic carbon fixed during meromixis. When combined with sulfate-reduction data, anaerobic respiration in the water column can mineralize 32–55% of this primary production. As lakes of this type approach salt saturation, As (V) can become the most important electron acceptor for the biogeochemical cycling of carbon.