Lactic dehydrogenase (LDH), a cytosolic enzyme found in neural and endocrine tissue, was measured in serum and tumor tissue of 15 patients with pheochromocytoma, a neuroendocrine neoplasm. Mean serum total LDH activity was higher in patients with pheochromocytoma than in patients with essential hypertension, normotensive control subjects, or those with various other categories of secondary hypertension. The prominent isoenzyme was LDH type 3. Their pheochromocytoma tissue, as well as normal human adrenal tissue, also contained LDH, maximally type 3; the amount of LDH in tumors far exceeded that in normal adrenal glands, suggesting that the tumor tissue is the source of the excessive serum LDH in these patients. While a large percentage of false-negative results (40%) does not render serum LDH activity a reasonable screening test for pheochromocytoma, and even though the true-positive rate is high (100%), we cannot yet recommend that hypertensive patients with high serum LDH activity undergo investigation for this tumor.