Guinea pig myelin basic protein (MBP) was inserted into phosphatidylserine liposomes and Lewis rats were injected by the intracardiac (ic) route with 75 microgram doses of MBP-liposomes according to various schedules. After challenge with 75 microgram guinea pig MBP in complete Freund's adjuvant, the rats were followed for clinical signs, were tested for delayed hypersensitivity (DTH) and lymphocyte transformation (LT) to MBP. The animals were sacrificed 30 days after challenge and the central nervous system tissue was examined for histological modifications. Rats treated with two injections of MBP-liposomes, 7 days before and 7 days after challenge, showed the highest degree of protection from clinical manifestations. Histological lesions were not significantly reduced. DTH reactions to MBP were all positive, regardless of treatment. LT assays were positive overall in only 50% of the animals tested. The response to rat MBP was significantly lower than to guinea pig MBP, especially in the groups treated with MBP-liposomes. Adoptive transfer of spleen cells from MBP-liposome-treated donors reduced the clinical scores of actively induced EAE in syngeneic recipients by 40-50%. These results suggest that at least one mechanism responsible for antigen-specific protection in EAE by MBP-liposomes operates through active suppression transferable by spleen cells.