The availability of fibroblast growth factor-2 (FGF-2) -deficient mice has permitted studying the role of endogenous FGF-2. Several studies have reported that neocortical but not hippocampal neurons are lost in FGF-2-deficient mice. Here, we show that neuronal densities within the basolateral amygdala are unaltered in FGF-2-/- mice. Moreover, we provide evidence that FGF-2 mutant mice display no obvious alterations in the catecholaminergic or cholinergic innervation of the hippocampus. With regard to the formation of dendritic spines, our studies reveal that endogenous FGF-2 is not essential for hippocampal spinogenesis; however, FGF-2 affects the length of individual spines. Such alterations in spine morphology may be related to disturbances in mental capacities or alterations in neuronal plasticity. Of interest, in this context, animal models of mental retardation develop no alterations in hippocampal spine densities, but display higher numbers of long dendritic spines. Thus, FGF-2 may also affect learning and memory by altering spine morphology.