IgG antibrain antibodies (ABA) of several specificities can be demonstrated in multiple sclerosis (MS) with the complement fixation technique. This technique seems to discriminate between IgG specifically and non-specifically bound to CNS preparations. Complement-fixing ABA were titrated in paired serum and CSF samples from 87 patients with clinically definite MS, 15 patients with probable MS, 29 patients with other neurological diseases, and 13 "healthy" controls. In addition, sera from 55 non-MS patients were tested. In 40% of the sera and 88% of the CSF samples from patients with clinically definite MS, ABA reacting with human brain homogenate were demonstrated. The corresponding figures for probable MS were 21% and 73%, and for the controls 11% and 6%. Two of 9 sera from patients with the Guillain-Barré syndrome were strongly positive. There was a tendency for higher CSF ABA titres in younger MS patients and in those with an earlier onset of disease. ABA titres in serum and CSF were both correlated with a more malignant course. Irrespective of the mechanism of induction of ABA in MS--an excessive immunogenic stimulation and/or a defective immunoregulation--they are potentially pathogenic in several ways, e.g. (1) by direct antibody action. (2) by interaction with complement, (3) by antibody-dependent K-cell-mediated cytotoxicity, and (4) by interaction with phagocytic cells. Of several correlations among the routine CSF variables in MS, the finding of more pronounced abnormalities in male patients was notable.