The effects of intravenous and epidural clonidine, 4 μg kg−1, combined with epidural morphine, 40 μg kg−1, on the neuro-endocrine and immune stress responses to thoracic surgery are reported. A control group received only epidural morphine. Anaesthesia was induced and maintained with propofol. Catecholamines, vasopressin, cortisol, β-endorphin concentrations and leucocyte counts were measured before drug administration, immediately after intubation of the trachea, after thoracotomy and at the end of surgery. Catecholamines did not change in any of the groups. The other stress hormones increased during surgery, the pattern being similar in the three groups. Total leucocyte and neutrophil counts were increased in all groups at the end of surgery, but the increase was least in the epidural clonidine group. The number of lymphocytes was reduced at the end of surgery in the epidural and intravenous group, compared with the control group in which the number of lymphocytes did not change. The effects are more pronounced with epidural than with intravenous administration. We conclude that clonidine can modulate the immune stress response to thoracic surgery.