In Experiment 1, ICR Swiss mice were exposed to one of two novel cages for 1, 6, or 10 30-min trials. Plasma corticosterone elevations were greater in the more novel than in the less novel cage and following the sixth as compared to the first and tenth exposures. In Experiment 2, BALB/c and C57BL/6J mice and Sprague-Dawley rats also exhibited significant, though modest, increases in corticosterone levels from their first to their sixth 30-min exposures to the more novel cage. These findings demonstrate generalization of an apparent sensitization of the plasma corticosterone response across the two levels of novelty and four strains of laboratory rodents tested here. The transience of the effect may explain some earlier inconsistencies in the literature. In Experiment 3, five daily 30-min exposures to the more novel environment minimally raised resting corticosterone levels of ICR Swiss mice. Further, corticosterone levels during a first exposure were no greater at 15 or 45 min than at 30 min. These results suggest that the increase in corticosterone with repeated exposures reflects a true sensitization of the corticosterone response rather than an increase in resting levels with repeated exposures or a shift in the time course of the corticosterone response.