The discovery of natural 210Po enrichment at levels exceeding 500 mBq/L in numerous domestic wells in northern Nevada, USA, led to a geochemical investigation of the processes responsible for its mobilization. 210Po activities in 63 domestic and public-supply wells ranged from below 1 mBq/L to 6590 ± 590 mBq/L, among the highest reported levels in the USA. There is little spatial or depth variability in 210Pb activity in study-area sediments and mobilization of a few percent of the 210Po in the sediments would account for all of the 210Po in water. Stable-isotope measurements indicate SO4 reduction has occurred in all 210Po contaminated wells. Sulfide species are not accumulating in the groundwater in much of Lahontan Valley, probably because of S cycling involving microbial SO4 reduction, abiotic oxidation of H2S to S0 by Mn(IV), followed by microbial disproportionation of S0 to H2S and SO4. The high pH, Ca depletion, MnCO3 saturation, and presence of S0 in Lahontan Valley groundwater may be consequences of the anaerobic S cycling. Consistent with data from naturally-enriched wells in Florida, 210Po activities begin to decrease when aqueous sulfide species begin to accumulate. This may be due to formation and precipitation of PoS, however, Eh–pH diagrams suggest PoS would not be stable in study-area groundwater. An alternative explanation for the study area is that H2S accumulation begins when anaerobic S cycling stops because Mn oxides are depleted and their reduction is no longer releasing 210Po. Common features of 210Po-enriched groundwater were identified by comparing the radiological and geochemical data from Nevada with data from naturally-enriched wells in Finland, and Florida and Maryland in the USA. Values of pH ranged from <5 in Florida wells to >9 in Nevada wells, indicating that pH is not critical in determining whether 210Po is present. Where U is present in the sediments, the data suggest 210Po levels may be elevated in aquifers with (1) SO4-reducing waters with low H2S concentrations, or (2) anoxic or oxic waters with extremely high Rn activities, particularly if the water is turbid.