Sera and cerebrospinal fluids (CSFs) from 66 patients selected from a larger sample of multiple sclerosis (MS) and control patients were studied for presence of complement-dependent cytotoxic (CT) antibody against baby hamster kidney cells infected with measles virus, strain Lec. The MS group contained 26 patients with clinically definite disease and 7 with probable MS. Seventeen of the 33 patients selected from the MS group had hemagglutination-inhibiting (HI) antibody to measles virus in their CSFs. Specimens from 33 control patients with other identifiable neurological disorders were matched according to the time of specimen sampling and with the age of the donors. Seven of the controls had HI CSF antibody. The serum CT geometric mean antibody titer of the MS group was approximately twofold higher than that of the control group. Forty-two percent of the MS group and 18% of the control group had CT antibody in the CSF. With the exception of the ratio of one control patient, the serum/CSF ratios of CT antibody from all patients were 128 or less. Nine CSFs (six MS and three control specimens) had CT antibody but no detectable HI antibody. Conversely, 12 CSFs (eight MS and four control specimens) had HI antibody but no detectable CT antibody. Five patients in the MS group with both kinds of CSF antibodies had reduced CT ratios but normal HI ratios. The results suggest that the two tests detect CSF antibodies reactive with different antigens. In this study, where less than half of the MS patients displayed CSF CT antibody, it is unlikely that such antibodies play an active role in the pathogenetic mechanism operative in the disease.