The co-stimulatory interactions of the B7 family molecules CD80 and CD86 on antigen-presenting cells, together with their T cell counter receptors CD28 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), modulate T lymphocyte-mediated immune responses in a reciprocal manner. To investigate whether there is altered expression and the clinical significance of soluble co-stimulatory molecules in asthmatic patients, plasma concentrations of sCTLA-4, sCD28, sCD80 and sCD86 in 51 adult allergic asthmatic adults with or without steroid treatment, and 35 sex- and age-matched control subjects were measured by enzyme-linked immunosorbent assay (ELISA). Cell surface expression of CTLA-4 and CD28 on peripheral blood mononuclear cells (PBMC) were analysed by flow cytometry. Results showed that the plasma sCTLA-4 concentration was significantly higher in all asthmatic patients while sCD28 and sCD86 concentrations were significantly higher in steroid and non-steroid treated asthmatic patients, respectively, compared with control subjects (all P < 0·01). Significantly increased cell surface expression of CD28 but not CTLA-4 on PBMC was found in asthmatic patients compared with controls (P < 0·05). The plasma concentration and cell surface expression of CTLA-4 were found to exhibit positive and significant correlations with those of CD28 (both P < 0·05). Serum total IgE concentration correlated positively and significantly with sCTLA-4 and sCD28 concentrations in allergic asthmatic patients (both P < 0·05). The increased expression of these soluble co-stimulatory molecules may reflect the dysregulation of T cell activation, thereby contributing to the immunopathogenesis of allergic asthma.