The aim of this study was to examine the effect of fexofenadine hydrochloride (FEX), a histamine H1-receptor antagonist, on nitric oxide (NO) production in-vitro and in-vivo. Nasal fibroblasts (5 x 10(5) cells per mL) were stimulated with 25 ng mL(-1) tumour necrosis factor-alpha in the presence of various concentrations of FEX. NO levels in 24-h-culture supernatants were measured by the Griess method and levels of inducible nitric oxide synthase (iNOS) mRNA levels in 12-h-cultured cells were measured by ELISA. FEX at more than 0.5 microg mL(-1) suppressed NO production from fibroblasts by inhibiting expression of iNOS mRNA. We also examined whether FEX could suppress NO production induced by lipopolysaccharide (LPS) stimulation in-vivo. BALB/c mice were treated with 5.0 mg kg(-1) LPS i.p. after daily oral doses of FEX, 1.0 mg kg(-1), for 1-3 weeks. Plasma was obtained 6 h later and NO levels measured by the Griess method. Expression of iNOS mRNA in lung tissues was measured by ELISA 6 h after LPS injection. Oral administration of FEX for 2 and 3 weeks, but not 1 week, significantly suppressed NO levels in plasma through the inhibition of iNOS mRNA expression, which were enhanced by LPS stimulation. These results suggest that the attenuating effect of FEX on NO production may be of therapeutic benefit in allergic diseases.