The present study examines whether autoimmune MRL-lpr mice develop impairments in learning and memory that correlate with changing severity of lupus-like disease. MRL-lpr mice (n = 20) were tested in the Morris water-maze at 12, 14, 16 and 18 weeks of age. Age-matched controls were congenic MRL +/+ mice (n = 20) that develop the disease much later. Immune status was assessed by the presence of anti-nuclear antibodies (ANA), brain-reactive antibodies, proteinuria, and haematocrit. Learning rates and memory retention did not differ between the substrains, and did not correlate or deteriorate with advancing age and autoimmunity. However, the baseline performance level in autoimmune MRL-lpr mice was shifted, as evidenced by a consistently longer task-solving latencies. Thigmotaxic swimming (along the pool wall) was pronounced in the MRL-lpr group, and was associated with the observed difference in performance. The present study does not support the notion that learning/memory abilities of autoimmune MRL-lpr mice are impaired per se, but may support the hypothesis that the rapid progress of humoral autoimmunity affects the emotionality of lupus-prone mice.