BACKGROUND: Hormonal vitamin D system affects the determination of T-cell responses. It is unknown if there is an association between vitamin D status and allergic conditions. Our aim was to investigate differences in serum IgE concentrations by vitamin D status [measured by 25(OH)D] and by a genetic variation in a key vitamin D activation enzyme (CYP27B1) previously shown to be associated with type 1 diabetes. METHODS: 9377 participants in the 1958 British birth cohort completed a biomedical assessment at 45 years of age ; 7288 eligible participants had data on 25(OH)D and IgE, with 6429 having further information on CYP27B1 genotype ()1260C>A). RESULTS: There was a nonlinear association between 25(OH)D and IgE (P-value for curvature = 0.0001). Compared with the reference group with the lowest IgE concentrations [25(OH)D 100-125 nmol/l], IgE concentrations were 29% higher (95% CI 9-48%) for participants with the 25(OH)D 135 nmol/l (adjusted for sex, month, smoking, alcohol consumption, time spent outside, geographical location, social class, PC/TV time, physical activity, body mass index and waist circumference). CYP27B1 genotype was associated with both 25(OH)D (difference for A vs. C allele: 1.88%, 95% CI 0.37-3.4%, P = 0.01) and IgE concentrations ()6.59%, )11.6% to )1.42%, P = 0.01). CONCLUSIONS: These data suggest that there may be a threshold effect with both low and high 25(OH)D levels associated with elevated IgE concentrations. The same CYP27B1 allele that is protective of diabetes was associated with increased IgE concentrations.