The pathogenesis of aspirin intolerance remains unclear. Inducible nitric oxide synthase (iNOS) expression is upregulated in nasal polyp epithelium, implying a role for nitric oxide (NO) in its formation. We decided to compare iNOS activity in polyp tissue from patients with and without aspirin intolerance. Nasal polyp tissue was collected from 15 patients undergoing routine nasal polypectomy. These patients were classified into three groups: Group A comprised patients with nasal polyps without asthma; Group B contained patients with nasal polyps and asthma; and Group C comprised patients with nasal polyps, asthma and aspirin sensitivity. All subjects in Group C had a history of aspirin-induced reaction and a confirmatory intranasal challenge with lysine-aspirin. NOS activity was measured by the ability of tissue homogenates to convert 3,4-L-arginine to L-citrulline in an L-N(G)-nitro-L-arginine-inhibitable fashion. The iNOS activity (picomoles) in polyp tissue from the 3 groups was: A, 248.72+/-220.79; B, 23.71+/-41.06; and C, 549.71+/-132.11. Thus, nasal polyps from patients with Samter's triad had a significantly higher iNOS activity (p = 0.004; one-way ANOVA). This finding does not correlate simply with disease severity or with the occurrence of asthma and could indicate another important facet of aspirin-induced airways disease.