Concern as to the toxicity of the oxides of nitrogen has been frequently expressed in clinical and toxicological literature. Oxides of nitrogen are highly reactive compounds and suggest toxic effects on biological systems. The earliest evidence for potential damage to man occurred in the chemical industry where as early as 1804 the death of a man and his dog was recorded after breathing nitric acid fumes. Other occupational exposures have been seen with the use of explosives which generated NO2 during misfires. Welding operations generate substantial quantities of NOx. Burning of plastics, shoe polish, and nitrocellulose also results in potentially excessive quantities of NOx. High concentrations of ambient NO2 were clearly associated with acute pulmonary edema and death. Lowry and Schuman were among the earliest investigators to demonstrate that exposures to NO2 in excess of 200 ppm. would induce the above effects. Their description of silo fillers disease clearly identified another potential occupationally related effect of NO2 exposure, but the disorder had been recognized much earlier when in 1914 four individuals died suddenly after entering a recently filled silo. These fatalities were mistakenly attributed to high concentrations of carbon dioxide.