Vitiligo is a depigmenting disorder characterized by the development of white patches with evidence in favour of an autoimmune mechanism. We investigated the role of melanotropins and the plasma levels of alpha-melanotropin and ACTH-like immunoreactivities in 40 vitiligo patients with the aim of detecting a possible influence of neuropeptide regulation of immunity. Twenty-one patients had active and 19 had stable vitiligo disease, 16 persons presented with an additional autoimmune thyroid disease. Median alpha-MSH levels in vitiligo patients were 6.4p mol/l [5.2;11.3] and significantly lower than in control persons with 11.4 pmol/l [8.6;13.4]. Median ACTH levels of the affected patient group were 17 pg/ml [10.5;28] and appeared statistically higher than 12 pg/ml [7;17] measured in the control group. Measured morning cortisol levels in both groups were not significantly different. Reduced cutaneous alpha-MSH immunoreactivities have been related to the development of autoimmune-induced depigmenting disorders. Our data present lower alpha-MSH plasma levels in vitiligo patients which may be associated with the development of vitiligo depigmentation and may indicate a condition of impaired peripheral tolerance in this autoimmune disorder.