Using in vivo scintigraphy with the 111In-labeled somatostatin analog octreotide, tumor localizations were demonstrated in 11 of 17 patients (65%) with medullary thyroid carcinoma (MTC). Tumor localizations in the liver in 7 patients, and in the thyroid in 1 patient were not detected on octreotide scintigraphy, most probably because of normal uptake of labeled octreotide in these organs. Specific somatostatin receptors were demonstrated in vitro on all 5 investigated tumors which had also been visualized in vivo, as well as on 1 tumor that was not. Immunohistochemically, somatostatin was present in 1 of 6 tumors that were visualized in vivo, and in neither of 2 tumors that were not. The ratio of serum calcitonin over carcino-embryonic antigen concentrations was significantly higher in patients whose MTCs were visualized during octreotide scintigraphy than in those whose tumors were not. We have formed the following conclusions: 1) In the majority of patients with metastatic MTC, tumor sites can be visualized using octreotide scintigraphy, although this technique is insensitive in detecting liver metastases or intrathyroidal tumor; 2) The visualization of MTC during in vivo somatostatin receptor imaging correlates with the in vitro presence of somatostatin receptors; 3) The immunohistochemical presence of somatostatin in the tumor does not seem to influence the outcome of in vivo somatostatin receptor imaging; and 4) Higher serum calcitonin over carcino-embryonic antigen ratios in patients whose MTC is visualized during octreotide scintigraphy might imply that somatostatin receptors are present on more differentiated MTC.