Abstract The isoenzyme, neuron-specific enolase (NSE) was evaluated as a serum marker for nonfunctioning pancreatic islet cell carcinoma. Serum NSE was measured by radioimmunoassay in 6 patients with islet cell cancer and in 22 healthy adults. Mean serum NSE in control subjects was 5 ng/ml (range 3.2 to 8.4 ng/ml). Three of six patients had clearly elevated serum NSE with values that ranged from 22 to 44 ng/ml. One patient had an equivocally elevated serum NSE of 9.2 ng/ml while receiving chemotherapy. When relapse occurred, the NSE level increased to 44 ng/ml. One of two patients with normal serum NSE had undergone radical pancreatectomy and had no evidence of disease when studied. Elevated serum NSE returned to normal limits after removal of all gross tumor in the only patient from whom a preoperative measurement was obtained. Results of this preliminary study suggest that serum NSE levels can aid in the diagnosis and monitoring of the course of nonfunctioning islet cell carcinoma.