Social stress by repeated defeat has been shown to be endowed with neuroendocrine and behavioural effects that render this stress model useful to identify adaptive mechanisms. Among these mechanisms, those related to central serotonergic systems (e.g., hippocampal 5-HT1A receptors, cortical 5-HT2A receptors) have been particularly underlined. Nonetheless, how (i) the neuroendocrine and behavioural effects of social stress are affected by the genetic status of the animal, and (ii) this status affects the relationships between central serotonergic systems and adaptive processes has not been studied so far. The present study has thus analysed the effects of repeated defeat (once a day for seven days) by Long-Evans resident rats upon the psychoneuroendocrine profile of Lewis rats and spontaneously hypertensive rats previously characterized for their contrasting social and anxiety-related behaviours. Repeated defeat decreased in a time-dependent manner, body weight growth and food intake in both strains, these decreases being, however, more severe and longer lasting in Lewis rats. This strain-dependent difference could not be accounted for by differences in physical contacts with the resident rats as the number of attacks and their latency throughout the stress period were similar between spontaneously hypertensive and Lewis rats. When exposed to an elevated plus-maze test of anxiety, the unstressed Lewis rats entered less the open arms than their spontaneously hypertensive counterparts, thus confirming that Lewis rats are more anxious than spontaneously hypertensive rats. This difference was amplified by stress as the latter increased anxiety-related behaviours in Lewis rats only. These strain- and stress-related differences were associated with differences in locomotor activity, this being increased in unstressed Lewis compared with spontaneously hypertensive rats; moreover, stress triggered hypolocomotion in the former but not the latter strain. Lastly, in the forced swimming test. Lewis rats spent more time immobile than spontaneously hypertensive rats with stress increasing immobility in a strain-independent manner. Beside the aforementioned metabolic changes, the activity of the hypothalamo-pituitary-adrenal axis was slightly stimulated in a strain-independent manner by the stressor, as assessed by increased corticosterone levels and adrenal weights, and decreased thymus weights. In Lewis, but not in spontaneously hypertensive rats, midbrain serotonin metabolism was increased by stress, a difference associated with an increased Bmax value of cortical [3H]ketanserin binding at 5-HT2A receptors. On the other hand, the Bmax value of hippocampal [3H]8-hydroxy-2-(di-n-propylamino)tetralin binding at 5-HT1A receptors was decreased by stress, this reduction being amplified in spontaneously hypertensive compared with Lewis rats. This study shows that the psychoneuroendocrine responses to social stress may have a genetic origin, and that the use of socially stressed Lewis and spontaneously hypertensive rats may provide an important paradigm to study adaptive processes. However, whether the aforementioned strain-dependent differences in central serotonergic systems (partly or totally) underlie the distinct profiles of emotivity measured in spontaneously hypertensive and Lewis rats, is discussed in the context of the relationships between serotonergic systems and behavioural responses to novel environments.