We evaluated the clinical and methodological features of the neuron-specific enolase radioimmunoassay (NSE RIA) (Pharmacia = Ph) with the neuron-specific enolase enzyme immunoassay (NSE EIA) on the ES 700 (Boehringer Mannheim = BM) and the NSE EIA on the Cobas Core System (Roche = Ro). A total of 253 serum samples obtained from 37 healthy persons, 45 patients with benign lung diseases, 124 patients with lung cancer (42 with small cell lung cancer, 23 with adenocarcinoma, 21 with squamous cell carcinoma, 11 with large cell carcinoma, and 27 with unknown histology), 34 with lung metastases, 7 patients with sarcoma and 6 patients with malign lymphatic diseases were stored at -80 degrees C and assayed retrospectively. The intra- and inter-assay imprecisions were lower for the automatized test systems than for the RIA. Correlation between the EIA's and the RIA was better for NSE (Ro) than for NSE (BM) (BM/Ph: r = 0.93 and slope = 0.54; Ro/Ph: r = 0.95, slope = 0.79), but weaker than the correlation between the two EIA's: over the whole range r = 0.96, neuron-specific enolase < 50 micrograms/l: r = 0.97, neuron-specific enolase < 20 micrograms/l: r = 0.92. Fixing the specificity at 95% versus benign lung diseases we found a cut off value of 11.9 micrograms/l for NSE RIA (Ph), 15.9 micrograms/l for NSE EIA (BM) and 13.5 micrograms/l for NSE EIA (Ro). Based on this specificity of 95% versus benign lung diseases as the clinically relevant reference group, the sensitivity for NSE RIA was 32% for all lung cancer and 45% for small cell lung cancer, for NSE EIA (BM) 35% for all lung cancer and 43% for small cell lung cancer, the NSE EIA (Ro) had a sensitivity of 42% for all lung cancer and 57% for small cell lung cancer. In a follow-up study of two patients with small cell lung cancer a good comparability for all three assays in the kinetics, but a marked difference in the neuron-specific enolase value levels was found. The results show that the NSE EIA (Ro) on Cobas Core system is the most sensitive assay for the detection of small cell lung cancer.