Endothelin family in human plasma and cerebrospinal fluid. To clarify whether endothelin may be present in human cerebrospinal fluid (CSF) and, if it exists, to compare its molecular forms with those of endothelin in human plasma, we analyzed pooled human CSF and plasma by high performance liquid chromatography with specific enzyme immunoassays for each endothelin peptide. Of the four human endothelin peptides hitherto identified, big endothelin-1 was the major molecular form of endothelin present in human CSF. In addition, there was a small but significant amount of endothelin-1 and endothelin-3 in CSF, while endothelin-2 was not detectable. Similarly, big endothelin-1, endothelin-1, and endothelin-3 were identified in human plasma. Although big endothelin-1 was the most abundant, a substantial amount of endothelin-1 and endothelin-3 was found in plasma with a resultant lower molar ratio of big endothelin-1 to endothelin-1 than in CSF. In all CSF samples from 17 patients requiring diagnostic lumbar puncture or lumbar anesthesia, endothelin was detectable, with a preponderance of big endothelin-1 relative to endothelin-1 and endothelin-3. The mean concentrations of endothelin-1 and endothelin-3 in simultaneously collected plasma were significantly (P less than 0.01) higher than those in CSF, while there was no significant difference between the mean big endothelin-1 concentration in plasma and that in CSF. There was no significant correlation among concentrations of big endothelin-1, endothelin-1, and endothelin-3 in each paired sample. These results indicate that endothelin is present in human CSF that is differently processed from endothelin in vascular endothelial cells and suggest a possible role for endothelin as a modulator of neuronal functions. 