Serum neuron-specific enolase (NSE) levels in 94 newly diagnosed untreated patients with small-cell lung cancer (SCLC) were compared with those in 30 adult controls. 38 of the SCLC patients had limited disease and 56 had extensive disease. Serum NSE was raised (greater than 12.0 ng/ml) in 69% of all patients (mean 52.35 +/- 11.56, range 4.1-850 ng/ml); it was raised in 15/38 (39%) of patients with limited stage disease and in 49/56 (87%) of those with extensive stage disease. Extensive stage patients had significantly higher mean NSE level (59 ng/ml) than did limited stage patients (13.8 ng/ml). Serum NSE was raised in 34/41 (84%) of patients with metastases at 1 or 2 sites and in all patients with metastases at 3 or more sites. Serial measurements in 23 patients receiving combination chemotherapy showed an excellent correlation between serum NSE and clinical response. Continuous cell-lines of SCLC, established from 10 of the patients in this study, all expressed high levels of NSE. These studies indicate that serum NSE may be a useful marker for staging and for monitoring response to therapy in patients with SCLC.