Atrial natriuretic peptide (ANP) is known to affect cardiovascular physiology displaying both hormone- and neurotransmitter characteristics. However, there is increasing evidence that ANP possesses additional biological activities referring to the immune system. To further strengthen this hypothesis the effect of ANP on two major functions of macrophages, i.e., phagocytosis and respiratory burst was tested. Both parameters were analyzed by flow cytometry employing bone marrow derived macrophages and the murine macrophage cell line J774. In both cell types preincubation with ANP dose dependently (10(-10)-10(-7) M) increases ingestion of opsonized fluorescent latex particles. The respiratory burst activity was monitored by oxidation of dihydrorhodamine-123 in cells stimulated either with phorbol-myristate (PMA, 10 ng/ml) or formyl-Met-Leu-Phe (fMLP, 1 microM). In both cases preexposure of cells to ANP (10(-8)-10(-6) M) for 2 h enhances reactive oxygen production. The data demonstrate an influence of ANP on important defense mechanisms of macrophages and thus extend the knowledge regarding the pharmacological profile of this natriuretic peptide.