The effect of Nesosteine, a novel mucolytic agent, on natural host resistance mechanisms was investigated in different organs of mice and rats. Single or repeated administrations of nesosteine by the i.v. or oral route (per os) were associated with significant increases in lung and spleen NK-mediated cytotoxicity, and in alveolar and peritoneal macrophages direct cytotoxicity. In both species the dose-response curve was bell-shaped, and optimal activity on both parameters seen at 1 mg/kg i.v. x 1, 100 mg/kg per os x 1 or 20 mg/kg per os x 5. Increases of at least 100% in lung NK and alveolar macrophages cytotoxicity were found in mice 48 h after single oral dosing at 100 mg/kg. The possible importance of Nesosteine immunostimulatory capacity in the activity of this compound in chronic hypersecretive bronchopulmonary disorders is discussed.