Abstract Methylmercury (MeHg) exposure can cause adverse health effects in children and adults and is predominantly from seafood consumption in the United States (U.S.). Here we examine evidence for differences in MeHg uptake and metabolism in U.S. individuals who consume three or more fish meals per week. We hypothesized based on prior research that some individuals have enhanced capacity to demethylate ingested MeHg and this will be reflected by a greater than typically observed δ202Hg offset in their hair relative to consumed fish (∼2 ‰). We used self-reported seafood intake data to identify individuals with hair Hg concentrations that agree extremely well with reported ingestion and those that do not. Approximately one-third of individuals in our survey population had hair Hg levels below the lower bound of probabilistic exposure modeling based on dietary intake data. The Δ199Hg values measured in the hair of a subset of individuals with the highest and lowest discrepancies between modeled and measured exposures are consistent with self-reported fish intake, validating the reliability of their dietary recall information. The δ202Hg offset between fish and human hair is similar for low- and high-discrepancy individuals, suggesting enhanced in vivo demethylation does not explain some individuals with hair Hg levels equivalent to non-fish consumers (0.10 ug/g). Using the probabilistic exposure model, we find dietary MeHg absorption efficiencies required to explain hair Hg levels in these high-discrepancy individuals are on average lower than 14% (range: 1%–72%). Exposure modeling for MeHg typically assumes a range of 91–97% and our results emphasize much greater inter-individual variability in this value.