BACKGROUND Environmental toxins, pathogens and host susceptibility cofactors may interact to contribute to disease. In vitro mercury exposure inhibited antiviral cytokines in human cells; however, little is known about the relationship between mercury and viruses in children. Children are susceptible to mercury toxicity; lower vitamin B-12 and folate levels and higher homocysteine levels may represent susceptibility cofactors. This study aimed to evaluate associations between total blood mercury (Hg) and measles antibodies in children, and the influence of these susceptibility cofactors. DESIGN Cross-sectional data on serum measles antibodies, Hg, homocysteine, methylmalonic acid (MMA, indicator of B-12 deficiency), and folate were obtained from the 2003-2004 NHANES for children aged 6-11 years with measles seropositivity (n=692). We used linear regression to evaluate relationships between measles antibodies and Hg, stratified by sex, MMA ≥, folate <, and homocysteine≥sample medians, adjusted for demographic, nutritional and environmental cofactors. RESULTS Hg (range: 0.10-19.10μg/L) was inversely associated with measles antibodies (range: 1.00-28.24 units) in non-stratified analysis (n=692), yet positively associated among the subset of boys with higher MMA and lower folate (n=98). Among this subset with higher homocysteine levels (n=61), correlations were positive across all Hg quartiles relative to Q1 (Hg≤0.20μg/L): Q2:β=6.60 (3.02, 10.19); Q3:β=8.49 (6.17, 10.81); Q4 (Hg>0.80μg/L):β=4.90 (2.12, 7.67) (p(trend)=0.077). CONCLUSION Stratification by susceptibility cofactors revealed opposing directionality for correlations between Hg and measles antibodies, with positive effect estimates at lowest exposures only among boys with higher MMA, lower folate and higher homocysteine levels.