Acute toxic inhalation by the oxidant gases, particularly ozone (O3), nitrogen dioxide (NO2) and oxygen (O2) at high tension, has been assumed to be no more than a chemical burn of the epithelial surface. More recently, oxidant toxic inhalation has been appreciated as a complex process involving biochemical, morphological and functional changes which are qualitatively similar although inducible by different agents. Recent advances in pulmonary pathophysiology, inhalation toxicology and particularly endothelial biology now challenge the validity of a theoretical framework which seemed almost complete just 5 years ago. Considerable attention has been paid in recent years to the biochemical events occurring at the moment of and immediately following exposure to the oxidant gases. Progress in elucidating the initial events has been rapid and promises a more complete picture in the near future. Studies of the pathophysiologic mechanisms associated with toxic inhalation by the oxidant gases have been relatively static, however. In this discussion, implications of recent findings in related fields were examined in an effort to identify new hypotheses and directions for investigation.