Recent studies have demonstrated an elevation of plasma soluble costimulatory molecules B7.1 (CD80) and B7.2 (CD86), and their T lymphocyte counter receptors cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and CD28 in asthmatic patients. We hypothesized that these costimulatory molecules may reflect the severity of asthma and investigated the longitudinal changes of these soluble costimulatory molecules, and their clinical significance in children with an asthmatic exacerbation. Sixteen children hospitalized for asthmatic exacerbation were recruited and treated with systemic corticosteroid (CS) for 5 days. Plasma total Immunoglobulin E (IgE) and eosinophil cationic protein (ECP) concentrations were measured by microparticle immunoassay and fluorescence enzyme immunoassay, respectively. Soluble CTLA-4 (sCTLA-4), sCD28, sCD80, and sCD86 concentrations in plasma were measured by enzyme-linked immunosorbent assay, and their relationships with asthma severity, total IgE, ECP concentrations, and blood eosinophil count were analyzed. Plasma sCTLA-4, sCD28, sCD80, and sCD86 concentrations in patients were highest during the acute attack. They decreased significantly with a parallel increase of peak expiratory flow rate (PEFR) after CS treatment (all P < 0.05). Plasma sCTLA-4, sCD28, and sCD86 concentrations of patients at recruitment were inversely correlated with PEFR, whereas plasma sCD28 and sCD86 concentrations correlated positively with eosinophil count and plasma ECP concentration (all P < 0.05). Although there was no such correlation with IgE concentration, sCD28 was correlated very significantly with eosinophil count (r = 0.83, P < 0.0001). In conclusion, plasma sCTLA-4, sCD28, sCD86, and sCD80 concentrations may reflect the severity of acute asthma and more studies on larger cohorts are needed to assess whether these markers are useful for assessing asthmatic exacerbation in children. Pediatr Pulmonol. 2006; 41: 674–682. © 2006 Wiley-Liss, Inc.