Earlier experiments indicated that chronic exposure to estradiol benzoate (EB) following septal lesions can increase the subsequent levels of female sexual behavior in male rats tested several months later following priming doses of EB. However, the present study demonstrates that a single injection of a large dose of EB (50 microng) two days after septal destruction did not modify subsequent responsiveness to EB priming in male rats relative to sham operated controls. Yet male rats given 10 daily injections of 5.0 microng EB/day immediately following a septal lesion were more responsive to EB than oil treated controls when tested later for lordosis behavior. Therefore, the capacity for EB to alter the behavioral effects of septal lesions on lordosis behavior in male rats is related to both chronic administration and a period of susceptibility to some action of EB during the immediate post-lesion period. In two additional experiments, chronic hypothyroidism induced by propylthiouracil or thyroidectomy was also found to modify the effects of septal lesions on female sexual behavior of male rats. These latter results indicate that EB is not unique in its capacity to alter the behavioral effects of septal lesions in male rats, and are consistent with the view that both EB and hypothyroidism may interact with some dynamic process associated with recovery from brain lesions.