Neuron-specific enolase (NSE) is an enzyme detectable in nervous and neuroendocrine tissue. Increased serum levels of NSE are found in small cell lung cancer and in patients with neuroblastoma, in whom NSE is used as a serum tumor marker. We have investigated 32 patients with histologically proven medullary thyroid carcinoma, a tumor of neuroendocrine origin, in which the classical tumor marker calcitonin (CT) was pathologically elevated. Positive immunocytochemistry for NSE and CT in C-cells was obtained in all cases. Increased serum NSE levels were found in only 5 of 32 patients, there was no correlation between NSE and CT concentrations. We also compared NSE and CT serum levels during long-term follow-up and again found no correlation between NSE and CT. After i.v. stimulation tests with pentagastrin and calcium, no correlation was found between NSE and CT serum levels. We conclude, therefore, that in medullary thyroid carcinoma NSE is useful for immunocytochemistry but not a reliable serum tumor marker.