Serum-ascites albumin concentration gradient, a parameter of oncotic pressure gradient reflecting presence or absence of portal hypertension, was compared with the usual parameters of ascitic fluid analysis in the differential diagnosis of ascites. Twenty-nine patients with liver disease and 15 patients with malignant neoplasm were prospectively studied. The group with malignant neoplasm showed higher ascitic fluid total protein level (3.70 +/- 1.28 vs. 1.66 +/- 1.20 g/dl), ascites to serum ratio of total protein level (0.58 +/- 0.14 vs. 0.26 +/- 0.14), ascitic fluid lactic dehydrogenase level (756 +/- 693 vs. 151 +/- 125 U/L), ascites to serum ratio of lactic dehydrogenase level (1.13 +/- 0.79 vs. 0.35 +/- 0.22), and lower serum-ascites albumin gradient (0.72 +/- 0.30 vs. 1.85 +/- 0.45) (p less than 0.001 for all parameters). Results of the serum-ascites albumin gradient overlapped the least between the two groups: all but 1 patient with malignant ascites while only 1 patient with liver disease had a gradient lower than 1.1. We conclude that the serum-ascites albumin gradient offers the best diagnostic discrimination between ascites caused by liver disease and ascites caused by a neoplasm.