Virus-like particles (VLPs) presenting conformational envelope proteins on their surface represent an invaluable tool to study molecular interactions between viruses and cellular receptors/co-receptors, eliminating biological risks associated with working with live native viruses. The availability of target cells expressing specific chemokine receptors facilitates the dissection of specific interactions between human immunodeficiency virus (HIV) viral envelope proteins and these receptors in the laboratory. Here, we describe a method to evaluate HIV-VLP binding to cellular chemokine co-receptors, by carboxyfluorescein succinimidyl ester labeling and cellular uptake.