Objective: Wheezing is a common symptom among children and is proposed to be associated with inflammatory cell infiltration, cytokines production, and with sonic risk factors such as gastro esophageal reflux (GER). The aim of the present study was to investigate endotheline-1 (ET-1) and leukotriene-E4 (LTE-4) levels, their response to steroid and beta 2-agonist therapy, and to establish if these parameters can be used as a diagnostic tool for infantile asthma and assess their relation with GER during acute attack of wheezy infants (WI). Material and Methods: Thirty WI and 12 healthy infants were enrolled in the present study. Serum IgE, ET-1, urine LTE-4 levels, and eosinophil percentage were measured prior to and 5 days after the treatment (systemic or inhaled steroid therapy and inhaled beta 2-agonist) in children with WI. In addition, esophageal pH was monitored for 24 hours. Results: Serum IgE, ET-1, and urine LTE-4 levels were significantly higher in the patients compared to the controls before and five clays after the treatment (p=0.009; p=0.039, p=0.032; p=0.014, p=0.017, respectively). The serum IgE and urine LTE-4 levels prior to and 5 days after the treatment were higher in the patients with GER when compared to the controls (p=0.021, p=0.016 and p=0.039). Moreover, the systemic or inhaled steroid therapy did not influence the serum ET-1 and urine LT-E4 levels. We found that the serum IgE and ET-1 levels on 5(th) day of the treatment and LTE-4 levels at the beginning and 5th day of the treatment were notably different in patients with higher likelihood for developing infantile asthma when compared to the controls. Finally, increased serum IgE levels were present in patients with good response to inhaled beta 2-agonist with regard to those with poor response to inhaled beta 2-agonist (p=0.031). Conclusion: The present study indicated that IgE, ET-1 and LTE-4 levels were related to airway inflammation in WI while LTE-4 and IgE levels were associated with GER. LTE-4 and IgE levels could be novel parameters for determining the risk factor for developing asthma in child with WI. Inhaled beta 2-agonist therapy seemed to be beneficial only in patients with high serum IgE levels.