It is well established that transforming growth factor alpha is involved prenatally in development of the nervous system, but its role in the postnatal brain is less well understood. Here, we document the occurrence of late-onset, morphological and behavioral deficits in the naturally occurring murine mutant, Waved-1 (Wa-1), whose transforming growth factor alpha levels decrease naturally between early postnatal and adolescent ages. Morphological analyses suggest that reduction in the growth factor postnatally is associated temporally with the onset of enlarged lateral ventricles, a reduction in vasculature in the region of the amygdala and a reduction in size of the central nucleus. Onset of the morphological deficits corresponds to the appearance of a performance deficit in contextual fear conditioning. In contrast, the transforming growth factor alpha gene-targeted null mutants exhibit neither morphological nor performance deficits. These data suggest that transforming growth factor alpha during postnatal maturation of the brain may contribute to maintenance of limbic morphology and vasculature, which may in turn affect some behaviors associated with these specific brain structures.