We measured human chorionic gonadotropin (hCG) and its subunits in 76 patients with islet-cell tumors. Seventeen of 27 patients with functioning islet-cell carcinomas had elevated plasma levels of hCG or one of its subunits (hCG-alpha and hCG-beta). Secretion was often discordant; the most frequent finding was an elevated level of hCG-alpha alone. In one patient responding to streptozocin, changes in hCG-alpha correlated with the clinical course. Studies of tumor extracts suggested that the markers observed in the circulation were being produced in the tumor itself. In contrast, none of the 43 patients with benign disease or the six patients with nonfunctioning malignant tumors had elevated levels of hCG, hCG-alpha or hCG-beta. These data show that hCG and its subunits are prevalent and specific markers for islet-cell carcinoma, and suggest that ectopic secretion results from malignant derepression of the genome rather than overproduction by an aberrant "cell rest."