This study was designed to investigate the presence of nitric oxide in human squamous cell carcinoma of the head and neck. We localized the activity of nitric oxide synthase in these tumors through immunohistochemical analysis using antibodies to L-citrulline (a byproduct of nitric oxide synthase), to inducible nitric oxide synthase, and to constitutive nitric oxide synthase. We found presence of inducible enzyme in squamous cells throughout these tumors, with the highest intensity staining occurring directly around keratin pearls. Our findings suggest that inducible nitric oxide synthase activity is present in squamous cell carcinomas of the head and neck, leading us to conclude that inducible nitric oxide synthase may play a significant role in tumor growth.