Background: We previously demonstrated that high doses of environmental cigarette smoke (ECS) induce alopecia in mice. This effect was prevented by the oral administration of N-acetylcysteine (NAC), an analogue and precursor Of L-cysteine and reduced glutathione. Objectives: The present study aimed at assessing whether L-cystine, the oxidized form Of L-cysteine, which is a key hair component, may behave like NAC in inhibiting ECS-induced atopecia and modulating the mechanisms responsible for this condition. Methods: C5713L/6 mice were exposed whote-body to ECS in a smoking machine. Groups of mice received in the diet, at three dose levels, a mixture Of L-cystine with vitamin B6, which plays a role in L-cystine incorporation in hair cells. Occurrence of alopecia areas and apoptosis of hair bulb cells were evaluated for up to 6 months of exposure, and the time Course induction of micronucleated erythrocytes in peripheral blood was investigated. Results: The frequency of micronucleated erythrocytes was increased by ECS, irrespective of treatment with L-cystine/vitamin B6. ECS-induced alopecia and apoptosis of hair bulb cells in all. exposed mice. L-Cystine/vitamin B6 inhibited alopecia in a dose-dependent fashion. Conclusions: High-dose ECS induces apoptosis-related atopecia in mice, and oral administration of L-cystine/vitamin 136 is an effective preventive treatment. (c) 2007 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.