Long-term arsenic exposure results in atherosclerosis and cancers, along with aberrant immune responses. Animal- based and epidemiological studies indicate that arsenic exposure increases susceptibility to viral and bacterial infections. This study aimed to assess whether arsenic exposure is associated with the development of fungal infection, which is substantially attributed to as a cause of aberrant immunity. Based on two well-established cohorts from two basins in southwestern (SW; high arsenic area) and northeastern (NE; low arsenic area) Taiwan (n = 297 and 2738, respectively), the arsenic exposure in well water was estimated using HPLC-ICP-MS. Fungal infections were defined via clinical and mycological assessments (PCR of fungal 18S rRNA) of nail samples. Individuals in SW cohort with cumulative arsenic exposure >10,000 mu g/L*years had a higher risk of developing fungal infections (OR = 1.57, 95% CI = 1.08-1.92) after adjusting for diabetes and occupation. In NE cohort, female sex, alcohol consumption, and chronic kidney diseases were associated with toenail infections. In contrast, fingernail infections (OR = 1.33, 95% CI = 1.05-1.68) were highly associated with arsenic exposure in a dose-dependent manner. We are the first to report palmar and plantar hyperkeratosis upon low arsenic exposure in 3.9% and 6.7% individuals, respectively. This is the first large-scale study showing arsenic exposure is associated with fungal infections in a dose-dependent manner. (C) 2016 Elsevier Ltd. All rights reserved.