In the serum of patients with malignant endocrine gastroenteropancreatic (GEP) tumours, both alpha-subunit (alpha-SU), common to all glycoprotein hormones, as well as free beta-subunit of human chorionic gonadotropin (hCG-beta) have been reported to be elevated in a substantial fraction. Both have been discussed as markers of malignancy in these neoplasms. In the present study we evaluated the diagnostic significance of alpha-SU and hCG-beta as serum markers in patients with malignant endocrine gastroenteropancreatic tumours. The study group consisted of 52 patients with endocrine GEP-malignancies (24 nonfunctioning, 23 carcinoid syndromes, four gastrinoma, one glucagonoma), located in the small intestine (n = 29), pancreas (n = 17), colon or rectum (n = 3), retroperitoneum (n = 2) and stomach (n = 1). alpha-SU and hCG-beta immunoreactivity was also assessed in the serum of patients with benign GEP-tumors (five insulinoma, and three gastrinoma). Concentrations of alpha-SU and hCG-beta were determined using two highly sensitive and specific immunoradiometric assays employing two monoclonal antibodies each. In 19 of 52 patients (37%), either alpha-SU (n = 9), hCG-beta (n = 7) or both subunits (n = 3) were elevated. In the subgroup of 24 patients with nonfunctioning GEP-tumours, increased concentrations of either alpha-SU (n = 6) or hCG-beta(n = 3) or both subunits (n = 1) were found in 10 of 24 patients (42%). In four of 23 patients with carcinoid syndrome (17%), either alpha-SU (n = 2), hCG-beta(n = 1) or both subunits (n = 1) were above the normal range. Of five patients with functionally active endocrine pancreatic islet cell tumours, all had an elevation of at least one of the two substances. In contrast, in the serum of all eight patients with benign GEP-tumours, alpha-SU and hCG-beta were within normal limits. In summary, our data show a high frequency of elevated alpha-SU or hCG-beta immunoreactivity in the serum of patients with malignant endocrine gastroenteropancreatic tumours. Since immunoreactivity is mostly discordantly elevated, the two markers are well suited to supplement each other. Absolute values had a similar range in the subgroups analysed. The prevalence was highest for functionally active endocrine pancreatic islet cell cancers, but nonfunctioning endocrine GEP-malignancies also exhibited a high frequency of predominantly alpha-SU immunoreactivity. This is important since this subgroup of endocrine GEP-tumours usually lacks hormonal markers. In patients with carcinoid syndrome, however, increased serum levels of alpha-SU or hCG-beta appear to be rare and of no diagnostic value.