Estrogen has been shown to affect the growth, differentiation, and survival of brain neurons and to modulate processes involved in synapse formation and connectivity. These trophic effects are diminished with aging as secretion of estrogen declines. The growth associated protein GAP-43 is found concentrated in axonal growth cones and is implicated in neuronal growth and regeneration. Previous studies have established that expression of GAP-43 can be modulated by estrogen in the preoptic area of developing and adult rat brain. This study was undertaken to determine whether this estrogenic regulation of GAP-43 mRNA is retained in aged rat brain. Young (3 months) and aged (24 months) rats were ovariectomized to remove endogenous estrogen and GAP-43 mRNA in the preoptic area was evaluated using in situ hybridization to compare estrogen and vehicle treatments between age groups. The results demonstrate an age-related decline in GAP-43 mRNA hybridization signal that can be restored to levels comparable to that seen in young animals with estrogen treatment.