Rhesus macaques were immunized with purified virus-derived simian immunodeficiency virus of macaques (SIVmac) 251/32H glycoprotein 130 (gp130) or primed with recombinant vaccinia virus (VV) expressing the env gene of the SIVmac BK28 clone and boosted subsequently with virus-derived gp130. High antibody titres of at least 10(4) against recombinant gp140 were induced with both vaccines. Analysis of the antibody specificity with a peptide ELISA revealed that different linear epitopes were recognized after administration of virus-derived gp130 compared with those after priming with VV. Antibodies to some epitopes (peptides 10 and 49), which were also found in SIV-infected animals, were induced with both vaccines, whereas antibodies to other regions were induced by only one vaccine preparation. The analysis of the helper T cell response revealed a poor immunogenicity of the virus-derived gp130, whereas priming with VV induced a considerable helper T cell activity in all three vaccinees after the second VV infection. Using synthetic peptides, several epitopes were identified. Our observations show that immunization with a virus-derived gp130 or live recombinant VV induces a considerably different antibody and helper T cell response. These differences in immunogenicity might have important implications for further vaccine development.