Oligoclonal bands (OCBs) were examined in CSF from 23 normal controls, 8 cases of inflammatory neurologic diseases, 24 cases of noninflammatory neurologic diseases, 27 sporadic cases of MS, and the 29 MS twin pairs, by isoelectric focusing followed by silver staining or western transblotting and immunoperoxidase staining. These methods are sensitive enough to detect as little as 25 ng of IgG. OCBs were detected in the CSF of 34 of 35 twins with clinical evidence of MS and in the CSF of 12 of 17 clinically normal twins. In some of these normal twins, the presence of OCBs in CSF antedated clinical manifestations of the disease.