['We tested the hypothesis that inducible nitric oxide synthase (iNOS) modulates angiogenesis in human models and this information could be extrapolated in elucidating the pathophysiology of oral submucous fibrosis (OSF). A hypothesis which looks inadequate, but is deep rooted in literature is the epithelial alteration ("atrophy") seen in OSF and the events that lead to its causation. This aspect was tried to be addressed and an alternative pathogenetic pathway for the disease is proposed.', 'This immunohistochemical study sought to investigate the expression of iNOS in OSF samples (n=30) a using monospecific antibody (SC- 2050, Santa Cruz Biotechnology, Inc) to the protein and also to correlate it with different grades of epithelial dysplasia associated with the disease. Twenty (20) healthy adults acted as controls.', 'iNOS staining was not demonstrated in normal oral epithelium. In oral epithelial dysplasia, staining was seen in all cases (100%) in the basal layers of the epithelium and in 30% of cases it extended into the parabasal compartments as well. iNOS staining was uniformly positive in moderate dysplasia with an increase in intensity and distribution noted as the severity of dysplasia progressed. There were highly significant differences in overall positivity for iNOS in epithelium between cases and controls (Mann-Whitney U=11.000, Wilcoxon W=221.00, P=0.000). Significant comparisons were made of mild Vs moderate dysplasia (Mann-Whitney U=48.000, P=0.014)'] Is inducible nitric oxide synthase expression upregulated in oral submucous fibrosis?