The effects of trichostatin A (TSA), a potent and specific inhibitor of mammalian histone deacetylase, on mouse teratocarcinoma cell (F9) differentiation were investigated.TSAcaused marked changes in the morphology of cells and stimulated the production of plasminogen activator within 24hr depending on de novo synthesis of RNAand protein.During the initial 6hr of incubation, a significant accumulation of hyperacetylated histone species was observed.These results suggest that histone acetylation due to inhibition of the deacetylase is involved in the early stage of morphological and biological differentiation induced by TSA.