Inositol phospholipid hydrolysis was examined in slices and synaptosomes prepared from area CA3 of control hippocampi and hippocampi in which long-term potentiation (LTP) was induced in vivo. In both synaptosomes and slices, LTP was associated with an increase in [3H]inositol labelling of inositol phosphates but not phosphoinositides. Glutamate (10(-3) M) significantly increased labelling of inositol phosphates in slices obtained from control tissue but had no effect either in slices obtained from potentiated tissue or in synaptosomes obtained from control or potentiated tissue. The finding that glutamate had no significant effect in slices prepared from potentiated tissue suggests that glutamate-mediated stimulation of inositol phospholipid hydrolysis in a postsynaptic compartment may be saturated in LTP. The possibility that the increase in phospholipid hydrolysis associated with LTP which we report here may be linked with the previously reported increase in transmitter release is discussed.