Background: Eosinophilic airways inflammation forms the pathophysiologic basis for a proportion of children at risk of developing recurrent wheezing. Early preventive measures and/or anti-inflammatory treatment may be guided by the identification of such children. Methods: We studied upper-airways inflammation by nasal lavage in a cohort of 397 infants within the first 4 weeks of life. They participated in an international multicenter study on the prevention of allergy in Europe (SPACE-Biomed II Program). A volume of 2 ml of prewarmed 0.9% saline was instilled into each nasal cavity and immediately re-collected by a suction device. The average recovery was 502 ml (SD: 311 ml). The concentrations of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were determined by RIA analysis. Results: ECP was detectable (>2 mg/l) in 47% of samples (173/365) and EPX (>3 mg/l) in 54.7% (197/360). Children with a doctor's diagnosis of a wheezy bronchitis within the first 6 months of life (n=40) had significantly higher ECP and EPX concentrations in the nasal lavage at 4 weeks of age (median ECP: 14 mg/l; 5-95th percentile: 0-122.4 mg/l) than children without such diagnosis (median ECP: 0 mg/l; 5±95th percentile: 0-86.6 mg/l; P<0.05). Corresponding figures for EPX were 12.14 mg/l (0-148.98 mg/l) vs 7.5 mg/l (0-81.46 mg/l; P<0.05). No associations between nasal ECP/EPX and the development of food allergy or eczema were observed. Conclusions: Increased nasal ECP and EPX in the first 4 weeks of life are associated with wheezing in 6-month-old infants at increased risk of atopic disease. We suggest that this might be related to a general tendency for a Th2 cytokine pattern in these young infants and subsequent trafficking of eosinophils into the nasal mucosa, or it might be a consequence of intrauterine allergen exposure.