Circulating levels of immunoreactive (i) PGE, calcium and parathyroid hormone (iPTH) were examined in 21 patients with neoplasia and 3 patients with primary hyperparathyroidism. Plasma iPGE was elevated in 4 of 11 hypercalcemic cancer patients; all extracts of liver metastases obtained from 3 of these 4 patients had elevated iPGE levels (metastases = 19.43 ± 3.43, n = 11; normal liver = 2.04 ± 0.23; ng/g tissue, × ± SE, P < .001). In contrast, only one of 10 normocalcemic cancer patients and none of 3 hyperparathyroid patients had elevated plasma iPGE. There were no apparent relationships between the presence of metastases and either hypercalcemia or elevations of plasma iPGE. Serum iPTH levels were undetectable or below the mean of the normal range in 19 of 21 cancer patients; only the three hyperparathyroid patients had elevated levels. Seven hypercalcemic patients were treated with indomethacin; plasma iPGE decreased in 6 (–34 ± 10% decrement, n = 6, P < .01). Decreases in serum calcium occurred only in those patients (2 of 6) who had abnormally elevated plasma iPGE prior to therapy. It is concluded that plasma iPGE elevations are found in some cancer patients, especially those with hypercalcemia, and that this marker may identify those patients who will respond to indomethacin treatment.