Macaques inoculated orally, vaginally, or parenterally with SHIV(KU-1) develop severe systemic infection, acute loss of CD4+ T cells, and AIDS. We showed in a previous report that passive immunization with neutralizing serum protected macaques against infection with parenterally inoculated pathogenic SHIV given 24 hr later. In the study reported here we asked whether the identical passive immunization protocol would protect macaques against infection with pathogenic SHIV following oral inoculation of the virus. Ten pigtail macaques were inoculated orally with one animal infectious dose of SHIV(KU-1). Four of the 10 had been given pooled anti-SHIV plasma (15 ml/kg) 24 hr earlier, 4 others were given the same dose of anti-SHIV plasma 2 hr after virus challenge, and the 2 remaining animals were used as controls. The neutralizing antibodies failed to protect macaques against infection after mucosal challenge with SHIV(KU-1).