Humoral antibody responses to Theiler's murine encephalomyelitis virus (TMEV) capsid proteins were examined. Rabbit antisera produced against the native BeAn strain of TMEV and against the isolated capsid proteins (VP1, VP2 and VP3) were tested for their ability to bind or neutralize virus and to inhibit the virus-induced haemagglutination of human O+ erythrocytes. Western immunoblotting analysis showed that isolated VP1, VP2 and VP3 each primed for a specific antibody response, but that native virions primed for antibodies specific for VP1 and VP2, but not VP3. Virus neutralization studies revealed that a dominant TMEV neutralizing determinant(s) lay on VP1, as did the haemagglutinating determinant. The possible location of the neutralizing epitopes are discussed on the basis of molecular modelling of the predicted amino acid sequence of TMEV from that of the closely related Mengo virus for which the three-dimensional structure is known.