BACKGROUND Numerous interactions exist among the nervous, endocrine, and immune systems, mediated by neurotransmitters, hormones, and cytokines. Melatonin may modulate the integrated functions of a unique neuro-immune-endocrine system. Neoplastic diseases may be linked to progressive loss of integration among these systems. We investigated whether there are differences among healthy elderly people and elderly people suffering from lung cancer at different stages of disease in 24-hour melatonin and cortisol secretory profiles. METHODS In seventeen healthy subjects (mean age +/-S.E.: 68.8+/-1.92 years), seventeen patients with stage I and II lung cancer (mean age: 67.2+/-0.80), seventeen patients with stage III and IV lung cancer (mean age: 69.5+/-2.26), melatonin and cortisol serum levels were measured in blood samples collected every four hours for 24 hours. The area under the curve (AUC) and the presence of circadian rhythmicity were evaluated. RESULTS The circadian rhythm of melatonin was present in all the groups, but serum levels were decreased in the subjects suffering from lung cancer (P<0.05). In these patients, cortisol serum levels were increased (not in a significant way), with a loss of the circadian rhythm of secretion. The melatonin/cortisol ratio was decreased in stage III and IV cancer patients (P<0.05). CONCLUSIONS The progressive decrease of melatonin secretion and altered cortisol secretion pattern with advancing stage of neoplastic disease may be an expression of a gradual alteration of the integrated function of the neuro-endocrine system in lung cancer patients.