Background: Urinary eosinophilic protein X (U-EPX) measurement is easy to perform in children. However, its use for prediction, diagnosis, and monitoring of asthma and atopy is unclear. Objective: We sought to investigate the relationship between U-EPX and clinical phenotypes suggestive of allergic diseases. Methods: U-EPX measurement (RIA), respiratory questionnaires, and skin testing were completed at age 3 years in 903 children followed prospectively from birth. Specific airway resistance was measured in 503 currently asymptomatic children by using whole-body plethysmography during tidal breathing. Results: Nonatopic children with wheezing or eczema had slightly increased U-EPX levels compared with nonatopic asymptomatic children. U-EPX levels (geometric mean EPX/creatinine ratio) were as follows: nonatopic asymptomatic children (n = 313), 61.3 μg/mmol (95% CI, 56.4-66.6 μg/mmol) ; nonatopic children with wheezing (n = 148), 71.2 μg/mmol (95% CI, 63.2-80. 1 μg/mmol); nonatopic children with eczema (n = 90), 65.7 μg/mmol (95% CI, 56.7-76.2 μg/mmol); and nonatopic children with wheezing and eczema (n = 86), 79.7 μg/mmol (95% CI, 67.4-94.3 μg/mmol). Children who had persistent atopy early in life had significantly higher U-EPX levels at age 3 years (nonatopic at 1 and 3 years [n = 263], 63.4 μg/mmol [95% CI, 58.4-69.0 μg/mmol]; atopic at 1 but not 3 years [n = 24], 65.1 μg/mmol [95% CI, 43.8-96.7 μg/mmol]; nonatopic at 1 year and atopic at 3 years [n = 62], 90.0 μg/mmol [95% CI, 74.6-108.4 μg/mmol]; atopic at 1 and 3 years [n = 35], 111.5 μg/mmol [95% CI, 89.2-139.3 μg/mmol]; P <.002). Atopy alone and with wheezing, eczema, or both was associated with significantly increased U-EPX levels (P <.0001). Wheezing appeared to be associated with higher U-EPX levels compared with eczema in both atopic and nonatopic children. The highest U-EPX level was found in atopic children with a history of wheezing and eczema (P <.0001). There was no relationship between U-EPX level and lung function. Conclusion: U-EPX level reflects the presence of atopy and associated symptoms and might be useful for monitoring the progression of allergic disease.