Ascitic fluid opsonic activity and ascitic fluid C3 concentrations are important protective factors against spontaneous bacterial peritonitis. This randomized controlled study was performed to compare the effect of diuretic administration alone vs. single large-volume therapeutic paracentesis followed by administration of diuretics on ascitic fluid opsonic activity and on ascites and serum immunoglobulin and complement concentrations in patients with alcoholic cirrhosis and tense ascites. Twenty-one patients were randomly allocated to two groups: group 1 included 11 patients who were treated with diuretics alone, and group 2 included 10 patients who were treated with single large-volume therapeutic paracentesis (5 to 6 L of ascites removed) followed by diuretics. Ascitic fluid opsonic activity and serum and ascites immunoglobulin and complement concentrations were measured at the beginning and at the end of treatment. The ascitic fluid opsonic activity increased significantly in patients treated with diuretics alone (p < 0.05), whereas in the group of patients treated with therapeutic paracentesis followed by diuretics, the ascites opsonic activity remained stable. Although ascitic fluid IgG, IgA and C3 concentrations increased significantly in patients treated with diuretics alone (p < 0.05), ascitic fluid C3 concentration significantly decreased in patients from group 2 (p < 0.05), whereas IgG and IgA concentrations remained unchanged. However, in both groups of patients serum immunoglobulin and complement concentrations remained unchanged. This study suggests that in cirrhotic patients with tense ascites, treatment with diuretics alone may have the potential advantage over single large-volume therapeutic paracentesis followed by the administration of diuretics of providing better protection from spontaneous bacterial peritonitis. However, further investigations are necessary to demonstrate the relevant clinical incidence of spontaneous bacterial peritonitis in cirrhotic patients with tense ascites treated either with diuretics alone or with single large-volume therapeutic paracentesis followed by diuretics. (Hepatology 1994;19:346–353).