Inhalation of swine confinement dust containing endotoxin causes an inflammatory response in the nose as reflected by an influx of neutrophils 3 hrs after exposure (Am J Respir Crit Care Med 149: A401(1994)). As there is evidence that nitric oxide (NO) in exhaled air indicates cellular activation, we studied whether endotoxin causes an increase in nasal NO production in human subjects. Seven healthy subjects underwent a nasal challenge in which 50 mg swine confinement dust was given into each nostril (endotoxin concentration, 23.6 microg . g-1). Exhaled NO was measured before and during 3 hrs after the challenge and was compared to control values measured over the same period of time. Endotoxin produced a slight but statistically significant (p = 0.017) increase in nasal NO concentrations, mean (+/-SEM) values over 3 hrs being 367.5 +/- 7.5 ppb after endotoxin and 342.1 +/- 7.2 ppb under control conditions. The difference was most pronounced during the first hour after the challenge. We conclude that nasal administration of endotoxin causes a short-term increase in NO production which must precede cell influx or upregulation of transcription.