An anti-HIV cream applied to the vagina or rectum could target the incoming virus and either permanently inactivate it or reduce its infectivity. Several promising molecules have been identified, but the topical efficacy of these compounds has been unclear. In the February 10 Nature Medicine, Ronald S. Veazey and colleagues at Tulane University Health Sciences Center, Covington, Louisiana, USA, show that vaginal administration of the broadly neutralizing human monoclonal antibody to HIV-1 gp120 (b12) can protect macaques from vaginal simian-human immunodeficiency virus (SHIV) infection (Nature Medicine DOI:10.1038/nm833, February 10, 2003).