HIV-1 entry into cells is mediated by the viral envelope glycoproteins gp120 and gp41. The first step in this process is the binding of gp120 to CD4 on the host cell surface. This interaction induces a conformational change in gp120 that exposes the binding site for a chemokine co-receptor. Novel insights into the molecular structure and function of this tripartite complex have now been provided by two recent papers. Kwong et al.[ 1 Kwong P.D. et al. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature. 1998; 393: 648-659 Crossref PubMed Scopus (2492) Google Scholar ]report the 2.5 Å resolution X-ray crystal structure of a truncated, deglycosylated gp120 `core' complexed with a fragment of CD4 and an antibody Fab fragment that overlaps the chemokine co-receptor-binding site. Several structural features are noteworthy. First, the CD4-binding pocket on gp120 is recessed. Second, 50% of the contacts are made with gp120 main chain atoms rather than with amino acid side chains. Thus, mutation of residues in the CD4 binding site allows the virus to evade immune recognition (usually made with side chains) but maintain interaction with CD4. The binding site on gp120 for chemokine co-receptors is distinct and does not overlap with that of CD4. This site is only revealed after CD4 binds to gp120. In addition, the site is so close to the target cell membrane as to limit potential antibody binding by steric hindrance. A final consideration is the assembly of gp120 and gp41 into a trimer. Wyatt et al.[ 2 Wyatt R. et al. The antigenic structure of the HIV gp120 envelope glycoprotein. Nature. 1998; 393: 705-711 Crossref PubMed Scopus (1070) Google Scholar ]note that the exposed surface area of the trimer is minimal, thereby protecting a large fraction of the gp120 surface against an antibody response. Taken together, these new data shed additional light on an area of HIV biology previously enveloped in darkness.