In the present study, the role of T-lymphocytes in the development of histaminergic hyperreactivity of the airways in vivo and in vitro, after intraperitoneal administration of bacterial endotoxin (1 mg/kg) to guinea-pigs was examined. Daily oral administration of the T-lymphocyte-selective immunosuppressive drug cyclosporin A (25 mg/kg) did not prevent the endotoxin-induced airway hyperreactivity in vivo. Cyclosporin A treatment itself induced histaminergic hyperreactivity of guinea-pig trachea in vitro. In cyclosporin A-pretreated guinea-pigs, endotoxin did not further potentiate the histaminergic responsiveness of isolated tracheal spirals. It can be concluded that T-lymphocytes do not play a role in the endotoxin-induced airway hyperreactivity in vivo. Furthermore, no definite conclusion concerning the involvement of T-lymphocytes in the endotoxin-induced hyperreactivity in vitro can yet be drawn.