MRL-lpr mice develop symptoms of autoimmune lupus-like disease early in the life and MRL(-)+/+ mice develop it substantially later. The present study examines our previous suggestion that autoimmune MRL-lpr mice show altered emotional reactivity. In addition, it aims to identify the set of measures which best discriminate the behavior of MRL-lpr mice from their congenic controls (MRL +/+). Behavior of males from these two substrains (n = 40/substrain; 3-4 mo of age) was compared on a battery of tests presumed to be reflective of emotional reactivity. MRL-lpr mice explored the open field less, spent more time at home-base, and defecated less in comparison to congenic MRL +/+ controls. Moreover, MRL-lpr mice hesitated to step down from an elevated platform and to make contact with a novel object. They also visited open-arms of a plus-maze less often and showed extensive floating in the Porsolt's swim test. Discriminant analysis revealed that the performance of the MRL-lpr and MRL +/+ mice differed most profoundly on measures taken in the Porsolt's swim and step-down tests. In addition, in the MRL-lpr group high titers of serum antinuclear antibodies were associated with impaired exploration of a novel object. These results are consistent with the previously proposed notion of increased "timidity" in autoimmune MRL-lpr mice and of an immune factor contribution to altered emotional reactivity. Considering that behavior of autoimmune MRL-lpr mice resembles behavior of stressed animals, it is speculated that disturbed emotional reactivity reflects the effect of autoimmunity on the hypothalamic-pituitary-adrenal axis.