Epstein-Barr virus (EBV) preparations from both NPC-KT cells (NPC-EBV) and P3HR-1 cells (HR-1-EBV) can induce cell fusion between EBV receptor (EBVR)-positive Raji cells and EBVR-negative cells, but other strains of EBV cannot induce cell fusion. The effect of these two EBV isolates on ability of cells to fuse has been studied to determine if there are differences in the biological properties of the different EBV isolates, particularly the isolates obtained from nasopharyngeal carcinoma such as NPC-EBV. The frequency of cell fusion between NPC-EBV-superinfected Raji cells and EBVR-negative epithelial cells (Ad-AH) was increased more than 30-fold in the presence of medium containing 1% dimethylsulfoxide (DMSO). However, the frequency of cell fusion between HR-1-EBV-superinfected Raji cells and Ad-AH cells was unaffected under the same conditions. The data show that differences in the ability of cells to fuse are induced by variants of EBV in response to DMSO. These differences may be important in elucidating the different biological properties of EBV isolates and might have implications for the pathophysiology of EBV-associated illness.