BACKGROUND: Adiposity is associated with high serum levels of adipokines and chemokines which are possibly implicated in a co-existence of obesity and asthma. OBJECTIVES: Elucidate the possible roles of leptin, interleukin (IL)-4, IL-5 and IL-21 in linking obesity with childhood asthma. DESIGN: Cross-sectional, analytical. SETTING: Population of schoolchildren in a small Saudi city. SUBJECTS AND METHODS: The study included a representative sample of Saudi schoolchildren grouped as obese asthmatics, nonobese asthmatics, or obese nonasthmatics, with nonobese nonasthmatics as a control group. An asthma control test was done for the asthmatic groups. MAIN OUTCOME MEASURES: Serum levels of leptin, IL-4, IL-5, and IL-21. SAMPLE SIZE: 345 male schoolchildren with a mean (SD) age of 13.0 (2.3) years. RESULTS: Median serum leptin concentrations in obese asthmatics were significantly higher than in nonobese asthmatics (P<.001). Uncontrolled asthmatics also had significantly higher leptin levels than controlled asthmatic children (P<.002). Leptin levels were weakly but significantly correlated with the cytokines IL-4, IL-5, and IL-21. CONCLUSIONS: Leptin may contribute to a link between obesity and childhood asthma. Differences in IL-21 levels between nonobese and obese asthmatics suggest that the co-existence of asthma and obesity increased IL-21 levels. Leptin plus some proinflammatory cytokines especially IL-21 may be potential predictors for asthma control in children. LIMITATIONS: Blood sampling at different stages of asthma might influence cytokine expression.