The concentration of subunits of hCG (hCG alpha and hCG beta) was determined in plasma or serum from 70 patients with primary hyperparathyroidism (1 degrees HPT). Two of three patients with parathyroid carcinoma showed elevation in plasma concentrations of both subunits, which fell after surgical removal of the tumor. An extract prepared from the tumor of 1 of these patients contained the subunits in high concentrations, whereas in extracts similarly prepared from tissues removed from 7 patients with benign 1 degrees HPT, the subunits were not detectable or were present in much lower concentrations. In 42 cases of benign 1 degrees HPT, samples from veins containing a 10-fold gradient of parathyroid hormone obtained during selective venous catheterization and peripheral samples from the same patients were analyzed for hCG subunits. Only 1 patient demonstrated a mild elevation of hCG alpha in parathyroid venous effluent alone that may have represented subunit release by apparently benign parathyroid tissue. Thirty patients with multiple endocrine neoplasia type I were tested; 8 evidenced clinically active islet cell tumors, and 6 of these 8 showed high circulating concentrations of hCG alpha (and hCG beta in 1 case). Patients in the multiple endocrine neoplasia type I group with 1 degrees HPT or pituitary tumors, but no evident pancreatic islet disease, did not show elevations in subunit concentrations. Thus, in patients with 1 degrees HPT, determination of subunits of hCG may be helpful in making the diagnosis of parathyroid carcinoma or in screening for associated (and probably malignant) pancreatic islet disease.