Brain-reactive auto-antibodies appear as key elements in the progressive CNS disturbances associated with systemic lupus erythematosus. The BxSB lupus prone mice are a model of this pathology, in which a gene located on the Y chromosome provokes a sex specific morbidity in males. This study was aimed to establish and characterize the relationships between behavioral disorders, neurological deficiencies and the aged-related immunological perturbations in this murine model. For this purpose, spatial and motor abilities were evaluated in male and female mice at six and 26 weeks of age. The results showed that the older males were greatly altered in their spatial abilities while the young ones and the females, whatever their age, were not. None of the animals had motor skill and motor learning disabilities. These spatial alterations were associated with modifications of basal neuronal activity measured by the cytochrome oxidase histochemical method in several areas directly or indirectly involved in spatial behavior, such as the hippocampus, the amygdala, the parietal and perirhinal cortex. Immunological study allowed us to correlate the behavioral abnormalities to the appearance of antibodies reactivities against cellular and nuclear components.