Background: Immune deficiency is a strong risk factor for non-Hodgkin lymphoma (NHL), but whether or not other forms of immune dysregulation are associated with NHL risk is unknown. We investigated associations between atopy, which is associated with a Th2-dominant immune response, and NHL risk. Because late birth order and childhood crowding are inversely associated with atopy, we also investigated their associations with NHL risk. Methods: We carried out a population-based case-control study among adults aged 20-74 years in New South Wales and the Australian Capital Territory, Australia. NHL patients without clinically apparent immune deficiency (N = 704) were selected from a cancer registry, and control subjects (N = 694) were randomly selected from state electoral rolls and frequency-matched to case patients by age, sex, and area of residence. Birth order, childhood crowding, and history of atopic conditions (hay fever, asthma, eczema, and specific allergies) were assessed by questionnaire and interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from logistic regression models that included the matching variables as covariates. Results: The odds ratios for developing NHL were 0.52 (95% CI = 0.32 to 0.84) for only children, 0.55 (95% CI = 0.40 to 0.75) for first-born children, 0.70 (95% CI = 0.51 to 0.96) for second-born children, and 0.81 (0.57 to 1.14) for third-born children (all compared with fourth- or later-born children) (Ptrend<.001). Indicators of crowding in later childhood, such as sharing a bed or bedroom, were not associated with NHL risk. A history of atopic conditions was associated with a reduced risk of NHL; this reduction was statistically significant for hay fever (OR = 0.65, 95% CI = 0.52 to 0.82) and food allergies (OR = 0.29, 95% CI = 0.20 to 0.42). Conclusions: Early birth order and its immunologic consequence, a Th2-dominated immune response, as reflected by a history of atopic disease, are associated with a reduced risk of NHL.