To examine the effects of long-term potentiation (LTP) on individual neurons in the intact brain, anesthetized rats were implanted with a recording stereotrode in the right CA1 layer of the hippocampus and a stimulating electrode in the right and left CA3 layers. The evoked and spontaneous firing of single CA1 neurons was characterized before and after LTP of the contralateral (commissural) Schaffer collaterals and again after LTP of the ipsilateral (associational) Schaffer collaterals. Individual CA1 neurons displayed either increases or decreases in evoked and spontaneous firing after LTP. As many as five discriminated cells were recorded simultaneously, and they typically responded discordantly, so that after LTP, firing in some neurons increased while in others it decreased. The response of individual neurons to in vivo LTP may be modulated by heterogeneous synaptic changes on individual and local groups of cells, and by changes in feed-forward excitation and inhibition provided by local hippocampal circuitry.