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Since Sachs and Steiner (1934) claimed to have demonstrated complement-fixing antibodies to brain in the serum of multiple-sclerosis patients, attempts to confirm and extend their findings have resulted in sharply divided conclusions. Some have agreed, culminating in the report by Raskin (1955), who has reported almost double their percentage of positives ; others, however, have not been able to find such antibodies at all. To decide between these conflicting observations is obviously important in the study of the pathogenesis of multiple sclerosis, especially since a humoral myelotoxic factor has recently been described in serum from animals with experimental allergic encephalitis (Bornstein and Appel, 1959). The present work was originally planned to follow the method of Raskin (1955), who has reported the greatest success, but this was quickly found to lead to technical difficulties in that results, both positive and negative, were not reproducible. Use of completely fresh (unfrozen) sera did not remove these inconsis tencies, and a detailed examination of the methods used by various authors was therefore made. As a result we believe that, to a considerable degree, discrepancies can be traced to variations in technical method ; of these, differences in the amount of complement used is the most important. Materials