The beta-adrenergic binding sites on splenic lymphocyte membranes of the guinea pig were characterized with the radio-ligand [125I]cyanopindolol and showed a maximal number of binding sites (Bmax) of 125 fmol/mg protein and an affinity (Kd) of 170 pM. The potency of various beta-adrenoceptor antagonists to compete for [125I]cyanopindolol binding suggested that the receptor is of the beta 2 subtype. Endotoxin (1 mg/kg) induced a 35% decrease in the number of beta-adrenergic binding sites on lymphocytes, 4 days after i.p. administration. The reduction in the number of beta-adrenoceptors on the lymphocytes was accompanied by a 30% decrease in the relaxation of isolated guinea pig tracheal spirals to isoprenaline and a 20% reduction in the number of beta-adrenergic binding sites in peripheral lung tissue. The endotoxin-induced deterioration of the beta-adrenergic system in the respiratory airways was completely prevented by splenectomy. It is concluded that the spleen, and or cells or products derived from the spleen, are involved in the changes of the beta-adrenergic system in the respiratory airways and lymphocytes.