We have studied the ability of gangliosides to induce or ameliorate experimental autoimmune encephalomyelitis (EAE) in Lewis rat and SJL mice. None of the animals immunized with gangliosides with or without methylated bovine serum albumin (MBSA) developed EAE. Gangliosides were also administered simultaneously with PLP, but they did not alter the incidence or severity of EAE. However, high doses of MBSA could ameliorate or prevent EAE in a dose-dependent manner. T-cell responses towards gangliosides and antiganglioside antibodies were also studied. In conclusion, in these experimental models gangliosides have no encephalitogenic activity and do not alter the course of EAE.