On examination in the first weeks after onset of the disease, an antibody-dependent lymphocyte cytotoxicity (ADLC) against myelin basic protein (MBP) was demonstrated in 32 (71%) of 46 patients with ON/only and in 8 of 10 patients with ON/MS. The findings were positive in 21 out of 22 CSF samples. The intensities of the cytotoxicity in the serum and in the cerebrospinal fluid were largely in agreement. No correlation was found between the cytotoxicity in the CSF and the IgG content. The ADLC against MBP is highly specific for MS. Only 5% of 200 patients with other neurological complaints had positive findings. Active disease phases in MS are positive in 94% of the cases according to earlier investigations. A positive ADLC against MBP in patients with ON/only is in all probability at first sign of MS.