The objective of our study was to determine thiol/disulphide homeostasis in recurrent aphtous stomatitis (RAS) patients. A prospective monocentric study was designed. Forty-three recurrent aphtous stomatitis patients and 43 healthy subjects were included to study. Venous blood samples collected and assessed with novel automatic system. Results compared statistically. Disulphide levels were found significantly higher in RAS patients than control group. There was no significant difference between native thiol and total thiol levels. Thiol/disulphide homeostasis is impaired in RAS patients in favor of disulphide levels compared with control group. To the best of our knowledge, the present study is the first examination on the correlation between thiol and disulfide homeostasis in patients with RAS. K E Y W O R D S recurrent aphtous stomatitis, thiol/disulphide homeostasis 1 | INTRODUCTION Recurrent aphthous stomatitis (RAS) is the most frequently seen painful intra-oral lesion. It generally starts in childhood or adolescence and recurs in the form of many small ulcers, which have round or ovoid borders on a yellow or gray base with erythematous surroundings. 1 The frequency and severity shows a decrease after the age of 50 years. In 1972, RAS were classified by Stanley in three groups as minor, major, and herpetiform. 2 Predisposing factors include genetic predisposition, oral trauma, hematological deficiencies such as iron, B12 and folic acid deficiencies, the use of ACE inhibitors, captopril and NSAIDs, inflammatory bowel diseases, celiac disease, oral hygiene products containing sodium lauryl sulphate, hormonal changes, and microorganisms. Recurrent aphthous stomatitis diagnosis is based on the history, examination, and histopathological features. Other causes of oral ulcers must be excluded. In 2004, Natah et al 3 defined a classification for minor RAS patients according to which they are separated as idiopathic and secondary. The causes of secondary RAS include Behcet's disease, MAGIC syndrome, PFAPA syndrome, Sweet syndrome, cyclic neutropenia, and HIV infection. Many biochemical markers have been used to reveal oxidative stress and inflammation, one of which is the thiol/disulphide balance. Dynamic thiol/disulphide homeostasis has an active role in many vital events such as programmed cell death, detoxification, antioxidant defense, cellular enzymatic activity, transcription, and cellular signal transmission mechanisms. When disulphide increases in the thiol/disulphide balance vital activities are affected and pathologies emerge leading to impairments in the function and structure of many organs. 4,5 Thiol groups form disulphide bonds under oxidative stress, and the conversion of thiols to disulphide bonds is seen as an early finding of increased oxidative stress. When the stress is removed the disulphide bonds revert to thiol groups. This formation and conversion process is known as thiol/disulphide homeostasis. 6 To the best of our knowledge, there has been no previous study which has evaluated thiol/disulp...