With a radioimmunoassay using hPTH 1-34 for antibody production, for radioiodination and as a standard, hPTH 1-34 was detectable (detection limit 40 pg/ml) preoperatively in peripheral blood in 14 of 29 patients with hyperparathyroidism, but in no controls. In all patients with parathyroid adenoma and detectable hPTH 1-34 preoperatively, the values fell after parathyroid surgery. Contrastingly, three of four patients with diffuse parathyroid hyperplasia and two of three with normal parathyroid glands showed a rise in hPTH 1-34 postoperatively, which was concomitant with very low serum calcium levels. In studies of hPTH 1-34 in central venous blood (3 patients), levels were detectable in all samples, but not in simultaneously drawn peripheral blood. Values for hPTh 1-34 in central blood correlated to PTH determined from a bovine assay, but the peripheral samples showed no correlation. The low levels of circulating N-terminal immunoreactivity in peripheral blood make this assay inapplicable for routine diagnostic purposes. These low levels are due not only to low secretion rates, but also to rapid peripheral metabolization.