It has been postulated that oxidative stress, nitric oxide (NO), and transforming growth factor beta(1) (TGF- beta(1)) have major roles in the pathophysiology of Crohn's disease (CD). The aim of this study was to determine the salivary levels of total antioxidant capacity (TAC), specific antioxidants (i.e., uric acid, albumin, transferrin, and thiol molecules), lipid peroxidation (LPO), NO, and TGF- beta(1) in CD patients and control subjects and to also investigate their correlation with activity of the disease. Twenty-eight patients with confirmed diagnosis of CD were enrolled and whole saliva samples were obtained. Smokers, diabetics, those who suffered from periodontitis, and those who were consuming antioxidant supplements were excluded from the study. The Crohn's Disease Activity Index (CDAI) was used to determine the severity of the disease. Twenty healthy subjects were also recruited. In CD patients significant reductions in salivary levels of TAC (0.248 +/- 0.145 vs. 0.342 +/- 0.110 mmol/L), albumin (1.79 +/- 0.42 vs. 2.3 +/- 0.2 microg/mL), and uric acid (3.1 +/- 1.4 vs. 4.1 +/- 2.0 mg/dL) were found. TGF-beta(1) was significantly increased in CD patients compared to healthy subjects (3.02 +/- 1.54 vs. 2.36 +/- 0.52 ng/mL). A fourfold increase in NO levels (198.8 +/- 39.9 vs. 50.2 +/- 21.3 micromol/L) along with a fivefold increase in LPO concentration (0.146 +/- 0.064 vs. 0.027 +/- 0.019 micromol/L) was documented in CD patients in comparison to the control group. CDAI significantly correlated with the TAC, LPO, and the interaction between TAC and LPO (r(2) = 0.625, r(2) = 0.8, F-test's P < 0.00005). Saliva of CD patients exhibits an abnormal feature with respect to oxidative stress, NO, and TGF-beta(1). TAC and LPO modify the effect of each other in determination of CD severity, which underlines the importance of oxidative stress in the pathogenesis of CD.