In order to test more specifically the role of the nucleus locus coeruleus (LC) in reaction to novelty, rats with bilateral 6-hydroxydopamine lesions of this nucleus, vehicle injected rats and non-operated animals were tested in the open-field and in the Hughes apparatus where motor activity is recorded in both a familiar and a non-familiar environment. In the open-field, the LC lesioned animals were significantly less active. A similar decrease of locomotor activity was observed in the Hughes test: the number of passages between the two boxes of the LC lesioned rats was significantly decreased. Likewise when the locomotor activities in the two boxes were pooled, the activity of the rats with lesions was significantly lower than the activity of the control rats, but in this case the locomotor deficit appeared only in the familiar box, the locomotor activity in the novel enclosure being the same in both LC lesioned and control animals. This result suggests that exploratory induced locomotion is not disturbed by the locus coeruleus lesion. The significant locomotor deficit showed by the LC lesioned rats in the familiar box could be due to an increased immobility induced by the stressful situation. Moreover, the deficit observed was the same whether the behavioral test began 4 days or 4 weeks after the lesion. Finally, at the end of the experiment, all rats were submitted to a moderate novel environmental stress and blood samples collected to measure the plasma levels of different stress hormones (ACTH, glucocorticoids, PRL, catecholamines). Hormone levels were the same in the LC lesioned and normal rats in spite of the fact that a significant loss of noradrenaline (53%) was observed in the hypothalamus of the rats with lesions. This result shows that the locus coeruleus is of minor importance in the control of stress induced neuroendocrine responses.