Pseudopregnant and normal cycling female Sprague-Dawley rats were trained on a delayed-spatial alternation task. After acquisition training, the subjects received frontal cortex lesions and were subsequently tested for retention. The pseudopregnant animals with lesions were less impaired than their normal cycling counterparts. Learning and retention testing were not affected by hormonal status in the noninjured controls. Histological examination showed that the normal cycling rats with frontal cortex lesions possessed enlarged ventricles, indicating the presence of edema in this surgical group. However, brain tissue of pseudopregnant subjects given the same lesion and sham operates of both hormonal states did not display this characteristic of edema. We speculate that the behavioral and anatomical impairment observed in the normal cycling females with brain injury is due to higher levels of vasopressin, a potent vasoconstrictor synchronized with brain injury in our manipulation.