It is known that administration of nerve growth factor (NGF) prevents the ocular dominance shift induced by monocular deprivation in the rat. To determine whether electrical activity in the visual afferent pathway is required for NGF effects on ocular dominance, we infused NGF into the cortex of animals subjected to complete monocular blockade of retinal discharges. Rats at the peak of the critical period received intravitreal tetrodotoxin (TTX) injections to silence activity in one eye for a period of 6-7 days; NGF was concurrently delivered into the visual cortex by means of osmotic minipumps. At the end of the treatment period, the ocular dominance distribution of cortical neurons was assessed by single-cell recordings. The results demonstrate that while infusion of NGF is effective in preventing the ocular dominance shift in lid-sutured rats, virtually no rescue can be observed in TTX-injected animals. Identical results were obtained when a specific agonist of the NGF receptor TrkA, the bivalent anti-rat TrkA IgG (RTA), was infused into the cortex in place of NGF. We conclude that NGF signalling via the TrkA receptor must be coupled to afferent electrical activity to produce its effects on the eye preference of cortical neurons. This suggests a generalized mechanism in which high-affinity neurotrophin receptor activation and afferent discharge interact to modulate neuronal plasticity in the developing visual cortex.