Human chorionic gonadotropin (hCG) is a clinically relevant marker of trophoblastic and nontrophoblastic malignancies. In the present studies, in addition to determining serum hCG, we investigated the presence and properties of hCG immunoreactivity in ascites of patients with nontrophoblastic malignant tumors and, for comparison, in ascites caused by cirrhotic liver disease. Total hCG immunoreactivity [hCG (+hCG-beta)] was found to be elevated above the reference value (greater than 5 IU/liter) in the serum of 2 of 20 patients with cirrhosis and 11 of 20 patients with malignant tumors. For comparison, in ascites, hCG (+hCG-beta) concentrations were frequently higher than in the corresponding serum samples and exceeded 10 IU/liter in 0 of 20 cirrhotic samples and in 16 of 20 malignant samples. In order to elucidate the nature of the hCG immunoreactive material, all samples were then assessed by immunoradiometric assays specific for the intact hCG molecule (holo-hCG) and the free hCG-beta subunit, respectively. In the holo-hCG assay, elevated values were detected in 0 of 20 (0 of 20) cirrhotic ascites (serum) samples and 0 of 20 (1 of 20) malignant ascites (serum) samples. In the free hCG-beta assay, on the other hand, no positive results were obtained in the ascites or serum of 20 patients with liver cirrhosis; however, 8 of 20 serum samples and 16 of 20 ascites samples derived from tumor patients were positive. In accord with the immunological data, gel chromatographical studies of malignant ascites revealed the abundance of free hCG-beta subunit rather than that of holo-hCG. In contrast to malignancy-related ascites, in ascites of patients receiving hCG injections for treatment of infertility, holo-hCG was more abundant than free hCG-beta immunoreactivity. Incubation experiments of purified holo-hCG in ascites for 24 h at -20, 20, or 37 degrees C showed no substantial dissociation of the hCG molecule and release of free hCG-beta immunoreactivity, thus arguing against production of free hCG-beta by degradation of holo-hCG and in favor of its tumor-related secretion. In conclusion, hCG-beta immunoreactivity is frequently elevated in malignancy-related ascites and appears to be related to the presence of free beta subunit of hCG rather than that of the intact hCG molecule. Interestingly, hCG-beta determination in ascites proved to be clearly superior to serum measurement in discriminating between tumor and cirrhosis.(ABSTRACT TRUNCATED AT 400 WORDS)