Epidemiological studies have consistently reported an inverse association between a history of allergic disease and risk of glioma. The reason for this association is unclear, and there is a lack of studies with the detail and size to explore the association in depth. We conducted a UK population-based case-control study with 965 glioma cases and 1,716 controls to investigate glioma risk in relation to allergic disease. Risk was reduced in subjects reporting a history of asthma (odds ratio (OR) = 0.71, 95% confidence interval (CI): 0.54-0.92), hay fever (OR = 0.73, 95% CI: 0.59-0.90), eczema (OR = 0.74, 95% CI: 0.56-0.97) and other allergies (OR = 0.65, 95% CI: 0.47-0.90). Risk was reduced for all the main histological groups. There was no significant trend of risk with age, at the onset of each condition, or the number of conditions reported. Risk reductions were strongest for asthma or hay fever with recent onset. Risk in asthmatic subjects was not related to frequency of use of antiasthmatic drugs, but was significantly reduced for use of antiallergenic medication among subjects with hay fever. The study showed an inverse association of glioma risk with allergic disease. Possible reasons for the association, as well as potential immunological aetiology, include confounding, bias and reverse causality.