The effects of two specific tyrosine kinase inhibitors on long-term potentiation (LTP) in the dentate gyrus were investigated using anesthetized rats. I.c.v. injection of herbimycin A (1.74 nmol) or lavendustin A (1.31 nmol) before application of tetanic stimulation significantly inhibited the formation of LTP. However, these inhibitors, when administered after tetanic stimulation, did not affect the established LTP. These results suggest that protein tyrosine phosphorylation is involved in formation of LTP at the dentate gyrus in vivo.