The effect of n-butyrate on superinfectability of virus-nonproducer Raji cells by the P3HR-1 strain of Epstein-Barr virus (EBV) was investigated. n-Butyrate is known to be a potent inducer of virus antigen synthesis in virus-producer cell lines and of cell differentiation in virus nonproducers. The drug inhibited the growth of Raji cells but did not interfere markedly with cell viability. It induced a low rate of early antigen (EA) synthesis in about 1-2% of noninfected Raji cells. While the number of superinfectable cells remained relatively constant after treatment with butyrate, an increase in antigen positivity was noted in untreated cells. This relative decrease in sensitivity to superinfection in butyrate-treated Raji cells was more pronounced in cultures that had been treated with the drug for 48 or 72 hr as compared to those treated for 24 hr. A blocking of the treated cells in the certain cell-cycle phase and their drug-induced differentiation towards plasma cells might have been involved in the phenomenon described.