Behavioral changes often accompany the autoimmune disease systemic lupus erythematosus (SLE) in humans and animals. In a mouse model of SLE, the NZB x NZW Fl (B/W) hybrid, 12-week-old mice display more anxiety behavior, less activity, and less exploratory behavior than non-autoimmune female NZW mice. To determine whether these behaviors result from the autoimmune disease or genetic differences between B/W and NZW mice, they were assessed prior to and during disease emergence (6 and 12 weeks of age, respectively). B/W mice were less active at both ages, suggesting a genetic component to this behavioral difference. Anxiety behavior and exploratory behavior did not differ between B/W and NZW mice at 6 weeks; however, at 12 weeks B/W mice displayed more anxiety behavior and less exploratory behavior, indicating that these behaviors were related with the development of autoimmune disease. Prior experience with these tasks increased anxiety behavior in B/W but not NZW mice, suggesting that B/W mice may be more sensitive to anxiogenic experiences. (C) 1996 Academic Press, Inc.