OM-85 BV, an immunomodulating preparation containing extracts from eight commonly pathogenic bacterial species, has been used with success as an oral adjuvant in the prevention of respiratory tract infections. Results from in vitro and in vivo experiments suggest various mechanisms that can underlie this beneficial effect. Thus, exposure of murine macrophages in vitro to OM-85 BV led to stimulation of biochemical and functional parameters associated with the disposal of microorganisms and tumor cells. Similarly, blood-derived human phagocytes were stimulated to express adhesion molecules (LFA-1, MAC-1, pl50,95, ICAM-1), to synthesize TNF-α and IL-2, and to develop a natural killer activity. These in vitro functions are reflected in the activation of immunological processes in vivo following administration of OM-85 BV per os. Oral treatment of mice and rabbits increased the capacity of the animals to clear bacteria from the blood, an effect that could be ascribed to enhanced functional activity of polymorphonuclear leukocytes. Administration of OM-85 BV per os also led to enhanced salivary IgA levels in man, and in gut and lung secretions in animals. Stimulation of migration and the beneficial effects of OM-85 BV correlated with phagocytosis-induced superoxide production in human bronchoalveolar lavage cells from orally treated individuals. Finally, injection of OM-85 BV was shown to enhance recovery from irradiation in animals, presumably by improving hemopoietic recovery. These findings indicate that OM-85 BV is capable of stimulating both cellular and humoral components of the immune response. In particular, administration per os promotes immune protective mechanisms active at the level of mucosal surfaces, thus providing a rationale for the oral prevention of acute exacerbations of chronic and recurrent respiratory tract infections using bacteria-derived immunomodulating agents.