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A radioimmunoassay for neuron specific enolase (NSE), a marker of neuroendocrine differentiation, has been evaluated in small cell lung cancer (SCLC). In untreated patients 25/38 (68%) with localized SCLC had raised blood levels of NSE (>13 ng ml-1), in extensive disease 34/39 (87%) patients had raised NSE levels. In patients with non-small cell lung cancer (NSCLC) the serum levels were raised in 16/94 (17%). In extensive tumours of non-pulmonary origin NSE levels were increased in 24/116 (20%) patients. Longitudinal studies indicated a good correlation between the response to chemotherapy and fall of NSE levels. Tumour progression was accompanied by a rising NSE in 25/29 patients, with doubling times of 7-90 days. In patients with progression with a normal NSE the recurrence was a NSCLC. Cerebral metastases occurring as the only recurrence during clinical complete remission were not accompanied by a rise of NSE. Serum NSE levels provides a valuable monitor for SCLC during and after chemotherapy. Enolase is a glycolytic enzyme [EC 4.2.1.11] that is composed of sub units a, ,B & y. Neuron specific enolase [NSE] is the yy dimer of enolase (Marangos et al., 1979). There is growing evidence that the histochemical demonstration of immuno-reactive neuron specific enolase (NSE) in tumour cells can be used as an indicator of their likely neural or neuroendocrine origin. Biochemically these cells are characterised as possessing amine precursor uptake and decarboxylation (APUD) enzyme systems and the production of various hormones and peptides. Tumours arising from the neuroendocrine cell system that contain NSE include, small cell lung cancer and medullary thyroid carcinoma (Lloyd et al., 1983). Several immuno-assay methods have been described for NSE in body fluids. The results of assays of serum NSE using the radioimmunoassay (RIA) devised by Marangos and his colleagues have been published for several types of tumours of neuroendocrine origin (Carney et al. Small cell lung cancer is the commonest type of tumour showing neuroendocrine differentiation.