Increasing interest is shown in the determination of the serum neuron-specific enolase for the diagnosis and the follow-up studies of small cell lung cancers. We report results obtained by an enzymatic procedure that permits the simultaneous determination of the neuron and nonneuron-specific enolase and the calculation of the ratio of these two components. The utility of this ratio which characterizes elevations of the serum neuron-specific enolase from a poor or rich source of this component was tested in 38 patients with small cell lung carcinoma and in 57 subjects suffering from other bronchogenic cancers. The control group consisted of 37 blood donors and 56 patients with respiratory disease. For the diagnosis, the sensitivity and the specificity of the enzymatically determined neuron-specific enolase compared well with published results obtained by radioimmunoassay and enzymoimmunoassay. The use of the ratio clearly increases the specificity of the test, since only 5.3 percent of false positive results are found when bronchogenic tumors other than small cell carcinoma are studied. The sensitivity was 76 and 100 percent in diagnosis of limited and extensive forms, respectively. The use of this ratio in the follow-up of the patients and for the determinations in hemolyzed samples is set out.