Creatine kinase (CK) and its BB isoenzyme (CK-BB) were measured in CSF in 65 evaluable patients suspected of CNS metastases secondary to small-cell lung cancer (SCLC). In addition, CSF and plasma levels of beta-2-microglobulin (beta-2-m) were measured in a group of 73 evaluable patients. Of the 65 patients analysed for CK-BB, 17 had meningeal carcinomatosis (MC), 26 had parenchymal metastases only, and 22 had no CNS disease. Patients with MC had a significantly higher CK-BB concentration in CSF than did patients belonging to the other two groups (P less than .01). Taking 0.4 U/L (upper limit in patients without CNS disease) as a cut-off point, 15 patients (88%) with MC had elevated CSF concentrations of CK-BB. Patients without CNS metastases had no CSF levels exceeding this value, whereas five patients with multiple CNS metastases did. Receiver operating characteristic (ROC) analysis suggests that CK-BB may be useful in distinguishing MC among patients suspected of having CNS metastases, and CK-BB appears superior to total CK, CSF protein, and CSF lactic dehydrogenase (LDH). In 12 patients with MC at autopsy, CK-BB was, with the above cut-off point, elevated in six patients with a false negative cytology. Of the 73 patients examined for beta-2-m, 18 had MC, 30 had parenchymatous metastases only, and 25 patients had no CNS metastases. The CSF concentrations in the three groups were not significantly different. The median concentrations in the groups were 133 nmol/L, 125 nmol/L, and 107 nmol/L, respectively. The ratios between beta-2-m in CSF and plasma were also not significantly different between the three groups. Thus, the data on CK-BB are promising, and further studies are warranted to see if the usefulness of CK-BB can be more firmly established. By contrast, beta-2-m has no role as a marker of CNS disease secondary to SCLC.