Two-dimensional electrophoresis, with isoelectric focusing in the first dimension and sodium dodecyl sulfate/polyacrylamide gel electrophoresis in the second, has been adapted for the high-resolution analysis of cerebrospinal fluid proteins. Proteins were detected with a new, highly sensitive silver stain that made visible more than 300 polypeptides from 60 microL of spinal fluid, in highly reproducible patterns. We have mapped these patterns, noting difference between the proteins observed in spinal fluid and plasma, and have prepared a partial map of cerebrospinal fluid proteins.