The encephalitogenic effects of bovine galactocerbroside and total myelin lipids given in the presence or absence of a known encephalitogenic dose of bovine myelin basic protein (MBP) in complete Freund's adjuvant have been examined in Hartley strain guinea pigs. The lipid haptens and MBP were given in the ratio in which they occur in intact myelin and were compared with experimental allergic encephalomyelitis (EAE) induced by whole bovine white matter in complete Freund's adjuvant. Clinically, bovine white matter- and MBP-induced EAE were similar, but in lesions in the central nervous system. Lipid/complete Freund's adjuvant emulsions were ineffective both clinically and histologically. In combination with MBP, galactocerebroside and total myelin lipids induced an EAE as severe as MBP-induced disease except that central nervous system lesions also showed demyelination. When given separately into opposite hindfeet, the lipid haptens and MBP produced EAE, but the lesions were not demyelinative. It appears, therefore, that lipid haptens have an augmenting effect on MBP when given in the same emulsion and produce central nervous system lesions which are both inflammatory and demyelinative.