On examination in the first weeks after onset of the disease, cell-mediated cytotoxicity against encephalitogenic peptide, myelin basic protein (MBP), cerebrosides and gangliosides was demonstrable in 32 (76%) of 42 patients with optic neuritis (ON). 14 patients with ON and concomitant neurological symptoms (ON/MS) had positive findings with all antigens, especially with the encephalitogenic peptide. The cytotoxic reactions against all antigens showed a close correlation with the course of ON: when the disease improved, the cytotoxicity decreased and became negative on average 4 months after ON onset. As previously reported, cell-mediated cytotoxicity against the above-mentioned antigens, especially the encephalitogenic peptide, may be considered as a pathogenetic factor in multiple sclerosis (MS). A positive reaction with this antigen in patients with ON only probably indicates the first manifestation of MS.