Lewis rats were immunized with recombinant vaccinia virus (VV) expressing the nucleocapsid (N), phospho (P), matrix (M), fusion (F), and haemagglutinin (H) proteins of measles virus (MV). Animals developed humoral as well as cell-mediated immune (CMI) responses to the corresponding MV proteins. Rats immunized with recombinants VVN, VVF or VVH survived a MV challenge infection whereas VVP- and VVM-immunized rats were only partially protected. In vivo depletion of CD8+ T lymphocytes did not prevent the protective effect of the N, F or H protein-specific CMI response in rats. VVH and VVF immunization induced neutralizing antibodies, but no such antibodies were detected after VVN immunization. Further investigation of the temporal occurrence of the antiviral antibodies indicated that the observed protection provided by VVN and VVF immunization depends on CD4+ N- or F-specific T cells in the absence of neutralizing antibodies and CD8+ T cells. A role for neutralizing antibodies induced by VVH cannot be ruled out.