Rats immunized with rat myelin basic protein (MBP) in an encephalitogenic regimen produce antibodies which cooperate with spleen cells from unimmunized rats in the specific lysis of MBP-sensitized chicken erythrocytes (MBP-CRBC) in vitro. Antibodies against MBP capable of participating in antibody-dependent cell-mediated cytotoxicity (ADCC) were detected in serum 9 days post immunization, and prior to the onset of experimental allergic encephalomyelitis (EAE). Measurements based on a sensitive radioimmunoassay technique had previously established that anti-MBP activity emerges by day 9, early enough to participate in events leading up to EAE. The ADCC assay was designed to further characterize functions of immunoglobulins associated with the humoral response to MBP, with emphasis on the cytophilic properties of early antibodies. The assay described was found to be nearly as sensitive as the RIA and could detect specific syngeneic rat anti-MBP at concentrations of about 0.03 pmoles/ml serum. Whether ADCC-type reactions take place in the central nervous system during acute EAE is not known; however, the presence of early cytophilic antibody in serum suggests that humoral immunity may play an ancillary role to that demonstrated for T-cell immunity in EAE.