Visna virus, a lentivirus of sheep, causes fusion of susceptible cells. Fusion has previously been shown to be mediated by the viral envelope glycoprotein. The transmembrane protein of visna virus contains a hydrophobic region at its amino terminus. This region is similar to the fusion epitopes of the orthomyxoviruses and paramyxoviruses. This region is located in a position similar to that of the fusion epitopes in the transmembrane proteins of HIV-1 and SIV. To determine the role of this hydrophobic region in visna virus-induced cell fusion, a peptide of 24 amino acids corresponding to this region was synthesized. The peptide alone induces fusion of goat cells. Antibodies to this peptide inhibit both viral-induced cell fusion and peptide fusion in goat cells. Further, the direct fusion of cells by this peptide is a unique observation and may be useful for studying the fusion epitopes of other lentiviruses. Thus, this hydrophobic region appears to be one epitope responsible for visna virus-induced cell fusion.