Serum concentrations of cancer antigen 125 (CA 125) were determined for 373 patients with various liver diseases: 57 with acute hepatitis, 57 with chronic hepatitis, 244 with liver cirrhosis (86 compensated and 158 decompensated), and 15 with primary liver cancer. The antigen was measured simultaneously in the serum and ascitic fluid of 46 of the patients with liver cirrhosis and sequentially in the serum and ascitic fluid of another 25 cirrhotics treated with paracentesis and (or) diuretics. Abnormal results for CA 125 were detected in sera from 4% of the patients with acute or chronic hepatitis, 60% of the patients with liver cirrhosis, and 67% of the patients with primary liver cancer. The main factor associated with abnormal serum concentrations of this antigen was the presence of ascites, with pathological CA 125 values in 94% of patients with ascites without jaundice (mean 566 +/- 528 arb. units/mL), compared with only 40% of patients with jaundice and without ascites (mean 40.1 +/- 28.5 arb. units/mL) (P less than 0.001). High concentrations of CA 125 were mainly associated with spontaneous bacterial peritonitis. The serum concentration of CA 125 decreased after treatment with paracentesis, but increased in patients treated with diuretics rather than paracentesis. The release of this antigen in liver cirrhosis appears to be independent of the liver disorder and, rather, results from peritoneal synthesis of this antigen.