Long-term potentiation (LTP) is generally divided into two phases, early (E-) and late (L-) LTP, of which only L-LTP is thought to depend on protein synthesis. Here we report that E-LTP can also be dependent on protein synthesis at higher levels of synaptic activation. Moreover, we show that the requirement for protein synthesis during L-LTP extends beyond the early induction phase and that it depends on synaptic stimulation. This suggests that the level of neuronal activity is a crucial determinant for the role of protein synthesis in E- and L-LTP.