We recently showed that peripheral blood cell supernatants from multiple sclerosis (MS) patients, containing reverse transcriptase activity and retroviral RNA from the newly human identified multiple sclerosis retrovirus (MSRV), also secrete a cytotoxin which induces death of primary mouse cortical glial cells. We have hypothesized that macrophages could release this cytotoxin in the cerebrospinal fluid. The cerebrospinal fluid cytotoxicity from 166 patients with various neurological diseases (including MS patients) was tested on glial cells in vitro. Our bioassay shows that a glial cytotoxic activity is significantly present in cerebrospinal fluid from patients with relapsing-remitting MS at relapse. Since this cytotoxic activity seems to correlate with active cases of MS, it may represent a critical pathogenic factor in the neuropathology of MS.