Nerve growth factor and its receptor(s) are present in several parts of the hippocampus (CA1, CA3, dentate gyrus) but nothing is known about their function in this area which plays a fundamental role in learning and memory processes. NGF delivered exogenously to hippocampal slices causes a concentration-dependent, marked reduction in the expression (but not the induction) of long term potentiation (LTP) without altering basal synaptic transmission. The effect is already half maximal at 0.05-0.1 ng ml-1 NGF, is reversible after removal of this growth factor, and is also detectable with a modified version of NGF which has lost its neurite outgrowth promoting activity in PC12 cells. These findings point to a role for hippocampal NGF as a possible modulator of learning and memory processes. Such modulation would be mediated by high-affinity receptors functionally distinct from those promoting morphological differentiation of PC12 cells and other NGF target cells.