Nerve growth factor (NGF) has been shown to regulate plasticity in the visual cortex of monocularly deprived animals. However, to date, few attempts have been made to investigate the role of NGF in synaptic plasticity at the cellular level. In the present paper we look at the effects of exogenously applied NGF on synaptic plasticity of layer II/III regular spiking (RS) neurons in visual cortex of 16-18 days old rats. We find that local application of NGF converts high frequency stimulation (HFS)-induced long term potentiation (LTP) into long term depression (LTD). We show that this shift of synaptic plasticity is also obtained with bath application of NGF during HFS. Application of NGF subsequent to HFS leaves LTP unaffected, conferring temporal constraints on NGF efficacy. NGF effects on LTP are mediated by TrkA receptors. Indeed, blockade of TrkA by monoclonal antibody prevents NGF from inducing LTD following HFS. Low frequency stimulation (LFS) elicits LTD in RS cells. We find that NGF or blockade of NGF signalling by anti TrkA antibody does not change the amplitude of the LTD induced by LFS. Thus, the NGF effect is selective for synaptic modifications induced by HFS in RS cells. The present results indicate that NGF may modulate the sign of long term changes of synaptic efficacy in response to high frequency inputs.