Milrinone (1 mg/kg i.m.), sildenafil (1 mg/kg p.o), and aminophylline (20 mg/kg i.m.) were administered to mice once or five times. The drugs increased the production of IL-1beta and NO by peritoneal macrophages. Milrinone or aminophylline did not change the percentage of phagocytosing cells. A single administration of sildenafil increased the percentage of phagocytosing granulocytes (after 12 h). Sildenafil administered five times decreased the percentage of phagocytosing monocytes (72 h after the last dose). A single administration of the drugs did not change the oxidative burst activity. PDE inhibitors administered five times temporarily enhanced the percentage of cells producing reactive oxidants.