Intronic transcriptional control sequences influence the cell-and tissue-specific expression of the CD21 gene. The interactions of such intronic control sequences, which are physically separated from the gene’s promoters, suggest that factors that alter chromatin structure might be influential in this process. Accordingly, we analyzed the effect of histone acetylation on the expression of CD21 in nonexpressing T and B lymphocytes, respectively. The acetylase inhibitors sodium butyrate and trichostatin A were used to create hyperacetylated histones. The CD21 gene was specifically activated in the previously transcriptionally quiescent cells in a time-and dose-dependent fashion: the expression of a number of other genes was not influenced. These data suggest a model of cell-type-specific deacetylase activity that serves to repress gene transcription when present and active.