The expression of activation molecules on peripheral-blood CD4 and CD8 T lymphocytes and the serum concentrations of two products of activated T lymphocytes [interferon-gamma (IFN-gamma) and soluble interleukin-2 receptor (sIL-2R)] were measured in patients with acute severe asthma (ASA) and controls. Significantly higher percentages of CD4+ cells from patients with ASA expressed IL-2R, HLA-DR and VLA-1 as compared to controls (p less than 0.01). In contrast, CD8+ cells from both asthmatics and controls did not express IL-2R and VLA-1, and their expression of HLA-DR in asthmatics was not increased. Serum concentrations of IFN-gamma and sIL-2R were significantly elevated in patients with ASA as compared to control groups (p less than 0.01). Concentrations decreased as the patients improved clinically following therapy. Significant correlations were observed between the improvements in airways obstruction and (1) the decreases in the percentages of peripheral-blood IL-2R+ T lymphocytes and (2) the decreases in serum concentrations of sIL-2R. These observations suggest that CD4 T lymphocyte activation is important in the pathogenesis of ASA.