Tyrosine kinases have been implicated in cellular processes thought to underlie learning and memory. Here we show that tyrosine kinases play a direct role in long-term synaptic facilitation (LTF) and long-term memory (LTM) for sensitization in Aplysia. Tyrosine kinase activity is required for serotonin-induced LTF of sensorimotor (SN-MN) synapses, and enhancement of endogenous tyrosine kinase activity facilitates the induction of LTF. These effects are mediated, at least in part, through mitogen-activated protein kinase (MAPK) activation and are blocked by transcriptional and translational inhibitors. Moreover, brain-derived neurotrophic factor (BDNF) also enhances the induction of LTF in a MAPK-dependent fashion. Finally, activation of endogenous tyrosine kinases enhances the induction of long-term memory for sensitization, and this enhancement also requires MAPK activation. Thus, tyrosine kinases, acting through MAPK, play a pivotal role in LTF and LTM formation.