Studies evaluating cell fusion by HIV indicate that optimal conditions for measuring this biological process involve the use of appropriate numbers of cells, the expression of HIV gp120 in infected cells, the presence of the CD4 protein on the surface of uninfected cells, and sugar moieties. Cellular metabolism and nucleic acid synthesis as measured by DNA, RNA and protein synthesis are not requires. Proteolytic enzymes eliminate virus fusion only when the uninfected cells involved in the process are treated. Since the CD4 protein remains on the surface of the treated cells, the structure of this receptor must be changed sufficiently so that it cannot participate in the fusion process. Alternatively, the results may indicate the elimination by trypsin of a specific fusion receptor.