The direct immunoperoxidase technique was used to assess IgG and IgM nuclear and cytoplasmic binding to the mouse brain as a function of age, brain damage, and stress. Nuclear IgM binding was found to increase in older animals (over 30 months of age). There was also heightened nuclear and cytoplasmic binding 1 week after a frontal cortex lesion in mice approximately 2 months of age. Mice with brain lesions, however, did not show greater binding some months later and, if allowed to die from natural causes, actually showed less IgM nuclear binding than control animals. No association was found between lifespan and binding or between stress per se and binding. The capacity of the blood-brain barrier to repair itself after injury is discussed, and these findings are compared to earlier data based on indirect measurement procedures.